bluuebunny/crossref_metadata_2025 huggingface dataset:
Binding of five monoclonal anti‐CEA antibodies with different epitope specifities to various carcinoma tissues
Authors: Wagener Christoph , Petzold Petra , Köhler Wolfgang , Totović Vladimir
Published: February 2007

Five monoclonal antibodies that recognize different epitopes on carcinoembryonic antigen (CEA) were reacted with tissue sections of various carcinoma specimens. The vital, non‐necrotic tissues of those carcinomas of the oesophagus, pancreas, colon and rectum, medullary thyroid, ovary and cervix in which CEA related epitopes were detectable bound all five antibodies to a similar degree. In 3/5 lung carcinomas, 2/10 mammary carcinomas and 1/5 gastric carcinomas, a significantly different binding of the monoclonal antibodies by vital tumour tissue was present as determined by three independent investigators. In necrotic tissue areas, heterogeneity of antibody binding was more common. In a previous investigation, it was shown that normal granulocytes and liver tissue differentially bind the monoclonal anti‐CEA antibodies, indicating the presence of crossreacting antigens. The equivalent binding of the five monoclonal anti‐CEA antibodies to most of the carcinomas tested suggests that this binding is due to the presence of complete CEA molecules and not only of crossreacting antigens.
Simultaneous hyperthermia at 43°c reduces radiation‐induced malignant transformation frequencies in golden hamster embryo cells
Authors: Watanabe Masami , Nikaido Osamu , Sugahara Tsutomu
Published: February 2007

Studies were done to determine whether hyperthermia alone, or in simultaneous combination with X‐rays, can induce malignant transformation in golden hamster embryo cells. Hyperthermia alone did not induce transformation. In fact, it reduced the frequency of the malignant transformation induced by X‐rays. DNA damage as measured by alkaline elution and protein degradation were both induced by hyperthermia. However, the relationship of such damage to cell death is not yet clear. Our data indicate that hyperthermia either alone or in combination with X‐ray treatment should be a safe method of cancer therapy.
Induction of epstein‐barr virus antigens by tumor promoters for epidermal and nonepidermal tissues
Authors: Takada Kenzo , Hausen Harald Zur
Published: February 2007

Fifteen established tumor promoters belonging to different chemical groups were tested for their ability to induce Epstein‐Barr virus (EBV)‐specific early antigens (EA) in EBV‐genome‐positive nonproducer Raji cells. Saccharin (a promoter in urinary bladder carcinogenesis), DDT (a promoter in liver carcinogenesis), anthralin and iodoacetic acid (promoters in skin carcinogenesis) gave a significant induction with a maximum of induced cells of 20% (8 mg/ml), 0.8% (20 μg/ml). 0.8% (100 ng/ml) and 0.7% (0.4 μg/ml), respectively. In addition, after combined application with a noninducing dose (0.2 ng/ml) of 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), seven additional tumor promoters induced 0.3‐2.1% EA‐positive cells two days after treatment. The results indicate that in addition to mouse skin tumor promoters such as diterpene esters, several compounds reported to possess tumor‐promoting activity in other types of tissue induce EBV. The data suggest that EBV induction is an effect commonly exerted by this group of compounds which should be very useful in screening for environmental tumor promoters.
The importance of 5‐HT for tumor cell lodgement in the liver
Authors: Skolnik G. , Bagge U. , Dahlström A. , Ahlman H.
Published: February 2007

Arrest and lodgement of circulating tumor cells in the microvasculature is a prerequisite for metastasis formation. Aggregation of activated platelets and subsequent release of bioactive substances seem to influence the lodgement process. Since thrombocytopenia has been shown to reduce lodgement and since 5‐HT is one of the compounds released from activated platelets, the present investigation was directed toward the influence of this amine on tumor cell lodgement in the liver after intraportal injection of fibrosarcoma cells. Lodgement was quantitated by an isotope technique with simultaneous measurements of 5‐HT levels by a LCEC technique in rat liver biopsies from areas with lodged tumor cells as observed with vital fluorescence microscopy. To test the importance of 5‐HT released from platelets, thrombocytopenia was induced with anti‐platelet serum in one experimental group, while animals in another group were treated with ketanserin (a selective 5‐HT2 receptor blocking agent). Animals given tumor cells alone showed a two‐fold increase in 5‐HT levels compared with animals injected with saline, indicating a relation between 5‐HT release and tumor cell lodgement. In thrombocytopenic animals lodgement was reduced to 53% (5‐HT levels reduced to 50%) of tumor‐cell‐injected controls. Ketanserin treatment reduced tumor cell lodgement to 72% (5‐HT levels to 63%). The results indicate that 5‐HT is one of the sub‐stances released from activated platelets and that 5‐HT is involved in tumor cell lodgement.
Variant generation and selection: An In vitro model of tumor progression
Authors: Chow Donna A.
Published: February 2007

Evidence for a new in vitro model of tumor progression was sought on the basis of the variant generation and selection hypothesis. The stability of a cloned murine tumor was examined during growth in standard tissue culture or in media containing the tumor promoter 12–0‐tetradecanoylphorbol‐13‐acetate (TPA). Analysis of subclones from the appropriate tumor populations revealed that growth of the L5178Y‐F9 clone in 100 ng/ml TPA and 0.1% dimethyl sulphoxide (DMSO) for 2 days yielded a tumor which exhibited increased cellular heterogeneity for susceptibility to both syngeneic and allogeneic natural antibodies (NAb). Subsequent exposure of TPA‐ and DMSO‐treated cells to two cycles of syngeneic NAb‐mediated cytolysis resulted in tumor populations which expressed a reduced sensitivity to syngeneic NAb. Thus the elements of tumor variant generation and selection were demonstrated by means of this approach, and repeated cycles of the TPA treatment and NAb cytolysis produced tumor cells with a reduced susceptibility not only to NAb in vitro but also to anti‐tumor natural resistance (NR) measured in a tumor elimination assay in vivo. These observations extend the support for the notion that tumor progression can proceed through variant generation and selection. Furthermore, the association of tumor variant generation with exposure to the combination of TPA and DMSO, both non‐mutagens, offers a model for studying non‐mutagenic mechanisms of tumor development.
Coffee drinking and the risk of epithelial ovarian cancer
Authors: Vecchia Carlo La , Franceschi Silvia , Decarli Adriano , Gentile Antonella , Liati Paola , Regallo Michela , Tognoni Gianni
Published: February 2007

The relation between ovarian cancer and coffee drinking habits was evaluated in a case‐control study of 247 histologically confirmed epithelial ovarian cancers and 494 agematched controls, admitted to hospital for acute conditions apparently unrelated to coffee consumption. Compared to rates for women who had never drunk coffee, the crude relative risk estimates for those who drank less than two, two or three, and four or more cups per day were 1.3, 1.5 and 1.4 respectively; however, when allowance was made for smoking habits, these risk estimates became 1.3, 1.7 and 1.8 respectively, and a significant linear trend of increasing risk with more elevated coffee consumption was evident. These results were not explained by various other potential confounding factors, including the major risk factors for ovarian cancer, but we had no information on dietary variables. The relative risk, however, did not increase with increasing duration of use. The findings of this study give apparent support in favour of the hypothesis that coffee consumption, or related dietary variables, may be associated with the risk of epithelial ovarian cancer. Further studies in different settings, however, are required in order to establish whether this association is real, and if so, whether it is causal.
Tissue type plasminogen activator, but not urokinase, exerts transformation‐enhancing activity
Authors: de Petro G. , Vartio T. , Salonen E. M. , Vaheri A. , Barlati S.
Published: February 2007

Previous studies have established that plasma cryoprecipitates of tumor patients, culture media of transformed cells and defined proteolytic fragments of fibronectin enhance the morphological cell transformation (TEF activity) in cultures of chicken embryo fibroblasts infected with temperature‐sensitive mutants of Rous sarcoma virus. We now report that purified human tissue type plasminogen activator (t‐PA), but not urokinase (u‐PA), has a similar TEF activity, at doses as low as 2 ng/ml (30 pM). Specific antibodies effectively neutralized the activity. No significant contamination (≤1%) between the preparations of t‐PA and fibronectin (FN) or its fragments (FNdp) was detected. The results suggest that t‐PA may have a direct role in the process of morphological cell transformation in vitro.
Calcium concentration defines two stages in transformation of lymphocytes by epstein‐barr virus
Authors: Moss D. J. , Burrows S. R. , Parsons P. G.
Published: February 2007

Lymphocytes from Epstein‐Barr virus (EBV) seronegative donors were either stimulated with Protein A or infected with EBV and cultured in growth medium containing a range of calcium levels (700 μM to <2 μM available calcium). Three calcium end‐points for the proliferation of B lymphocytes were defined: 18 M for mitogenicallystimulated B cells; 8 μM for a pre‐12 h event in EBV transformation and <2 μM for a post‐12 h event in EBV transformation resembling the end‐point for the emergent lymphoblastoid cell line. EBV‐infected lymphocytes cultured in calcium‐depleted medium expressed the EB virus nuclear antigen and proliferated after addition of calcium chloride. The present study should be useful both in defining the sequence of events in EBV transformation and in studying properties specific to the transformed phenotype.
Primary but not metastatic human melanomas expressing dr antigens stimulate autologous lymphocytes
Authors: Fossati Giuseppe , Taramelli Donatella , Balsari Andrea , Bogdanovich Gordana , Andreola Salvatore , Parmiani Giorgio
Published: February 2007

Lymphocytes from melanoma patients were stimulated in mixed culture with autologous tumor cells (MLTC) in order to evaluate lymphocyte proliferation and subsequent cytotoxicity on autologous melanoma cells. It was found that melanoma cells from lymph node metastases were unable to induce autologous tumor‐cytotoxic cells in 21 cases examined, in 15 of which MLTC also failed to induce lymphocyte proliferation. Patients' lymphocytes, however, were significantly stimulated by allogeneic irradiated lymphocytes and by interleukin 2. To investigate whether the lack of autologous stimulation was restricted to metastatic cells, the immune response of patients with only primary lesions of malignant melanoma was evaluated. It was found that primary melanoma cells were able to induce proliferation in 7 out of 9 (77%) patients, whereas positive cytotoxicity was obtained in 2 out of 4 patients tested. In order to see whether the presence of DR molecules was important for the stimulatory activity, melanoma cells were examined for the expression of DR antigens by indirect immunofluorescence with monoclonal antibodies. Positive autologous MLTC was found in all of six DR+ primary melanomas, whereas the two DR‐tumors were unable to stimulate autologous lymphocytes. An anti‐DR but not an anti‐DC monoclonal antibody was able to block the proliferation of lymphocytes induced by an autologous primary melanoma. Neither MLTC nor cell‐mediated killing was obtained with either DR+ or DR‐metastatic melanoma. In 60% of the cases tested, however, DR+ metastatic melanoma cells were able to stimulate allogeneic lymphocytes of normal individuals. Increased expression of DR antigens was induced by in vitro treatment with human gamma‐interferon in metastatic tumor cells; this caused an increase in the proliferation of allogeneic but not autologous lymphocytes. These findings indicate that primary but not metastatic DR+ melanoma cells are able to activate the proliferation and cytotoxicity of autologous peripheral blood lymphocytes, suggesting a potential role of DR antigens in regulating tumor‐host relationships in melanoma patients.
Establishment of an etoposide‐resistant human epithelial tumour cell line In vitro: Characterization of patterns of cross‐resistance and drug sensitivities
Authors: Hill Bridget T. , Bellamy Angela S.
Published: February 2007

A human tumour cell line resistant to etoposide (VP16–213) has been produced by fractionated X‐irradiation exposure in vitro. Characterization of this line, derived from an epithelioid carcinoma of the tongue, revealed no significant differences in terms of several cytological and kinetic parameters compared with the parent line. Patterns of cross‐resistance and drug sensitivities were determined by colony formation in soft agar after 24 h drug exposures. Three patterns of response were observed with the VP16–213‐resistant cells showing: marked cross‐resistance to vincristine and tenopside, collateral sensitivity to 5‐fluorourcil, hydroxyurea and cis‐platinum, and comparable responses to the parent line for adriamycin, bleomycin, dibromodulcitol and methotrexate. This is the first demonstration that specific drug resistance can be induced by prior exposure to X‐irradiation in vitro. This cell line appears to show a unique lack of cross‐resistance between adriamycin and vincristine or etoposide. Preliminary investigations into possible mechanisms of etoposide resistance demonstrated similar DNA sedimentation profiles after etoposide exposure in both tumour cell lines, implying no differential effects of this drug on DNA of resistant cells. These data raise the possibility that the expression and mechanism of resistance may differ, depending on the manner in which drug resistance is induced.
M2, A novel myelomonocytic cell surface antigen and its distribution on leukemic cells
Authors: Majdic Otto , Bettelheim Peter , Stockinger Hannes , Aberer Werner , Liszka Kristof , Lutz Dieter , Knapp Walter
Published: February 2007

The selectivity of a novel myelomonocytic cell surface antigen, designated M2, has been assessed in a series of 208 leukemias. The M2 antigen is defined by a monoclonal antibody (VIM‐2) of the IgM class. Its expression within the normal hemopoietic system is restricted to myelomonocytic cells. Lymphocytes, erythrocytes, thrombocytes and their morphologically recognizable precursors are negative. Sixty of the 66 acute myeloblastic leukemias (= 91%) and 28 of the 30 myeloid blast crises of CML patients (= 93%) were M2‐positive. As expected from our findings with normal myeloid cells, the myeloid cells found in stable phase of CML were also in all instances, M2‐positive. Quite in contrast, lymphoid cells from patients with B‐CLL, T‐CLL, prolymphocytic leukemia, hairy‐cell leukemia, lymphoblastic lymphoma, Sézary syndrome, from CML patients in lymphoid blast crisis and from the majority of patients with ALL, were completely M2‐negative. Also negative were the blast cells of patients with acute megakaryoblastic leukemia and acute erythroleukemia. A direct comparison of M2 expression with the display of the 3‐fucosyl‐N‐acetyllactosamine determinant, the structure recognized by most of the anti‐myeloid monoclonal antibodies reported so far, shows that more AMLs are M2‐positive and the proportion of M2‐positive blast cells in individual AML samples is higher.
Monoclonal antibodies identify a cea crossreacting antigen of 95 kD (NCA‐95) distinct in antigenicity and tissue distribution from the previously described NCA of 55 kD
Authors: Buchegger Franz , Schreyer Magali , Carrel Stephan , Mach Jean‐Pierre
Published: February 2007

During the selection of monoclonal antibodies (MAb) raised against purified carcinoembryonic antigen (CEA), two MAbs were identified which immunoprecipitated a glycoprotein of 95 kD present both in perchloric acid extracts of normal lung and on the surface of normal granulocytes. This antigen was distinct from the previously reported normal glycoprotein crossreacting with CEA (NCA) which had a molecular weight of 55 kD. The difference between the smaller and the larger crossreacting antigens termed NCA‐55 and NCA‐95, respectively, was demonstrated by SDS‐polyacrylamide gel electrophoresis, by elution from Sephadex‐G200 and by selective binding to a series of anti‐CEA MAb. Out of six MAb which all bound CEA purified from colon carcinoma, three did not react with these two crossreacting antigens, one bound only NCA‐95, one reacted only with NCA‐55 and one reacted with both NCA‐55 and NCA‐95. Immunoadsorbent purified preparations of 125I labelled NCA‐95 and NCA‐55 were found useful for the screening of new anti‐CEA MAb. In addition, when tested on frozen sections of colon carcinoma, normal spleen, normal lung and pancreas, each type of MAb gave a clearly different pattern of reactivity. The three anti‐CEA MAb which did not bind any of the crossreacting antigens stained only the colon carcinoma cells; the MAb binding to either one of the two types of NCA gave a similar pattern of reactivity both on colon carcinoma cells and on granulocytes. However, on normal lung and pancreas, the MAb binding NCA‐55 stained granulocytes as well as bronchiolar and alveolar epithelial cells in lung and inter‐ and intra‐lobular duct epithelial cells in pancreas, whereas the MAb binding only NCA‐95 stained only the granulocytes. Thus, the newly identified NCA‐95 appears to differ from NCA‐55 not only in terms of molecular size and antigenicity but also by the fact that in normal lung and pancreas it is found in granulocytes but not in epithelial cells.
Characterization of In vitro immunoselected variants from a highly metastatic murine tumor for alterations in malignant behavior in vivo
Authors: Liteplo R. G. , Frost P. , Donaghue T. P. , Kerbel R. S.
Published: February 2007

A new Ly‐6.2− antigen‐loss variant (called L61‐MI) of the highly metastatic DBA/2 mouse (Ly‐6.2+) MDAY‐D2 tumor has been obtained by means of a monoclonal anti‐Ly‐6.2 antibody in an in vitro immunoselection technique. Whereas L61‐MI grew poorly when inoculated subcutaneously into the syngeneic host, it grew and metastasized in a similar way to the parental MDAY‐D2 tumor when inoculated into immunosuppressed, athymic nude mice. L61‐MI as well as another Ly‐6.2− variant of the same MDAY‐D2 tumor (called L61) which is poorly metastatic in the syngeneic host salvaged exogenous fucose into glycoproteins and glycolipids at rates 5.5 and 7.8 times that of the parental MDAY‐D2 line. In contrast, the Ly‐6.2− variants exhibited a 50–70% decrease in the incorporation of exogenous mannose into glycoproteins and glycolipids. L61‐MI and L61 also exhibited alterations in the structures of the oligosaccharide moieties linked to the cell surface glycoproteins and/or glycolipids. Thus, the in vitro immunoselection technique can be used to obtain a panel of variants with stable phenotypic alterations in their growth and metastatic capacities. Such mutants may, like previously described lectin‐resistant mutants, be useful in studying the contribution of cell surface glycoproteins and glycolipids to tumorigenicity and metastasis.
Cytotoxic action of retinoidal butenolides on mouse neuroblastoma and rat glioma cells
Authors: Higashida Haruhiro , Miki Naomasa , Ito Masayoshi , Iwata Tsutomu , Tsukida Kiyoshi
Published: February 2007

Proliferation and death were measured in cultures of mouse neuroblastoma N18TG‐2 and rat glioma C6BU‐1 cells when treated with up to 100 μM retinoidal butenolides (RB 1‐6). The number of viable cells in each case was measured with various concentrations of the compounds, of which RB‐3 (5‐hydroxy‐4‐[2‐(2,6,6‐trimethyl‐1‐cyclohexen‐1‐yl) ethenyl]‐2(5H)‐furanone) was the most potent in destroying the cells after 2 days' incubation. ED50 of RB‐3 was about 5 × 10−7 M for both types of cell. RB‐3 was 80 times more potent than retinoic acid. Ten analogues of RB‐3 had a similar inhibitory effect on DNA synthesis in N18TG‐2 cells. The degenerative changes caused by RB‐3 in C6BU‐1 cells were irreversible even when the cells were exposed to it for 2 h. Tumor weights of N18TG‐2 cells that had been inoculated subcutaneously onto the backs of A/J mice were 30‐40% lower than those of untreated controls after 14 days of single daily i.p. injections of RB‐3 doses of 100 mg/kg of body weight. The results indicate that RB‐3 is cytotoxic in murine tumor cells originating from the nervous system and has an inhibitory effect on neuroblastoma‐tumor growth in mice.
Substances that can trigger activation of the alternative pathway of complement have anti‐melanoma activity in mice
Authors: Cooper Peter D. , Sim Robert B.
Published: February 2007

Intraperitoneal (i.p.) injection of substances that can ignite the alternative pathway of complement, namely isolated human C3b or C3(H2O), guinea‐pig C3(H2O) or cobra venom factor, or conventionally prepared zymosan, will reproducibly and very significantly increase the mean survival time of C57BL mice previously inoculated i.p. with melanoma cells. The effect is greater at higher doses and earlier post‐inoculation (p.i.) administration, but the substances are active at low doses (30–100 μg/mouse) if given early enough. It is likely that C3b or C3(H2O) was the previously unidentified anti‐tumour factor activated in serum by S. aureus treatment or serum fractionation and described elsewhere. Activation of the alternative pathway of complement appears to have potential interest for cancer therapy.
Properties of a herpesvirus‐transformed hamster cell line: Immunogenicity of sublines of high and low metastatic potential
Authors: Teale David M. , Rees Robert C. , Clark Anthony , Potter Christopher W.
Published: February 2007

The immunogenicity of a herpesvirus hominis type‐2‐transformed hamster cell line (HSV‐2–333–2–26) of low spontaneous metastatic ability was compared with that of its two in vivo‐derived sublines of increased metastatic potential. The parent (HSV‐2–333–2–26) tumour was immunogenic as assessed by protection against tumour challenge afforded by implantation of irradiated tumour cells or tissue. In contrast, the two metastatic sublines, designated Met A and Met B, were non‐immunogenic as defined by the above critera. However, the parent Met A and Met B tumours were shown to possess a common antigen(s), since immunization with irradiated parent tumour cells afforded protection to challenge with Met A or Met B. Immunization with the metastatic sublines, however, gave no protection to homologous or heterologous tumour challenge. Bacillus Calmette‐Guérin (BCG) inoculated in admixture with irradiated tumour cells and followed 7 days later by one immunization with X‐irradiated tumour cells alone, increased host immunocompetence to subsequent homologous or cross‐tumour cell challenge with parent, Met A or Met B cells. The immunity raised by using BCG plus irradiated tumour cells was shown to be specific to antigens expressed on the HSV‐2 parent cell line and its metastatic sublines. In addition, BCG admixed with live inocula of parent, Met A or Met B cells induced contact suppression of in vivo tumour growth of the parent cells, but not of Met A or Met B cells. It is suggested from these studies that the parent tumour possesses a tumour‐specific transplantation antigen(s)(TSTAs) which is not functionally active on its metastatically derived sublines. Common antigens, shared between the parent and Met A and Met B cells, are detectable by cross‐challenge experiments, but they themselves appear not to be immunologically offensive. The loss of immunogenicity is discussed as a possible mechanism for the in vivo selection of sublines with increased metastatic potential.
Transformation of atla‐negative leukocytes by blood components from anti‐ATLA‐positive donors In vitro
Authors: Miyamoto Kanji , Tomita Noriko , Ishii Akio , Nishizaki Takeshi , Kitajima Ko‐Ichi , Tanaka Toshio , Nakamura Takashi , Watanabe Sekiko , Oda Takuzo
Published: February 2007

Anti‐ATLA‐positive blood components transformed healthy human leukocytes in vitro. Blood components examined were packed red cells, whole blood, platelet concentrate and fresh frozen plasma. Leukocytes present in anti‐ATLA‐positive blood components such as packed red cells, whole blood and platelet concentrate easily transformed anti‐ATLA‐negative leukocytes. Co‐culture in fresh frozen plasma, however, did not transform recipient leukocytes, and leukocytes of anti‐ATLA‐positive recipients proved refractory to transformation. The transformed cells were morphologically lymphoid, grew in suspension, and possessed normal recipient karyotypes except in the case of three platelet concentrates. A high proportion of all the transformed populations formed Erosettes with neuraminidase‐treated sheep erytrocytes. The cytoplasm of over 90% of each recipient was stained brilliantly with antibodies against ATLV‐determined antigens. Electron microscopy of these transformed cells revealed many C‐type virus particles in the extracellular space. Blood components, such as packed red cells, whole blood and platelet concentrate, containing leukocytes from anti‐ATLA‐positive donors, should be used cautiously to prevent the transmission on ATLV to anti‐ATLA‐negative recipients.
Isolation of htlv derived from japanese adult T‐cell leukemia patients in human diploid fibroblast strain IMR90 and the biological characters of the infected cells
Authors: Yoshikura H. , Nishida J. , Yoshida M. , Kitamura Y. , Takaku F. , Ikeda S.
Published: February 2007

HTLV was isolated in the human diploid fibroblast strain IMR90 directly from the leukemic cells of the Japanese ATL‐patients. The infection was checked by the presence of virus‐specific p24 and proviral DNA. The isolation was successful in three of four patients. The patient whose virus isolation was unsuccessful contained only a defective viral genome in his leukemic cells. The infected cells produced polykaryons when co‐cultured with catS+L‐cells. Human leukemia HL60 cells formed clusters adherent to the infected IMR90 cells but not to uninfected IMR90 cells. The former phenomenon was blocked by the ATLL patients' serum.
Imbalance of helper and suppressor T lymphocytes in malignant non‐hodgkin lymphomas: An In situ morphometric analysis
Authors: Gattringer C. , Huber H. , Radaszkiewicz T. , Pfaller W. , Braunsteiner H.
Published: February 2007

The number and distribution of reactive T cells within 100 malignant B‐cell lymphomas were evaluated in situ by immunomorphometry using stereological methods. Findings were related to histological and clinical parameters. A mean of 2 × 104 reactive T cells/μI tumour tissue was found. This corresponds to 40% of the T‐cell content of normal lymphatic tissues. The distribution of reactive T cells within the tumours was diffuse except for centroblastic/centrocytic lymphomas. When evaluating the different histological entities a correlation between number of helper T cells, T helper:T suppressor (TH:TS) ratio and histological subgroups emerged, particularly in non‐Hodgkinlymphomas of low‐grade malignancy. The highest ratio was found in prognostically favourable subgroups, CLL(2.7 ± 0.3) and tumour areas of centroblastic/centrocytic lymphomas (2.9 ± 0.4). In contrast, a significantly lower ratio was found in centrocytic lymphomas (1.4 ± 0.3) corresponding well to the worst prognosis of this subgroup. The relationship between the number of helper T cells in tumour tissues, TH:TS ratio and prognosis was confirmed and extended by the evaluation of clinical data. It could be shown that, independently of histological criteria, a close correlation exists between the number of T cells, particularly T helper cells within the tumour, TH:TS ratio and clinical course. Patients with a favourable course had 1.4 × 104 T helper cells/μI tumour tissue compared to only 0.8 × 104 for patients with an unfavourable clinical course (p<0.01); the TH:TS ratio was 2.8 for the favourable and 1.8 for the unfavourable group, respectively (p<0.04). In contrast, neither treatment nor tumour stage had a clear‐cut influence on the extent of T‐cell infiltration.
Unequal forms of 140–110 kD glycoproteins in B16 melanoma cells with differing detachment properties and metastatic behavior: Influence of bromodeoxyuridine
Authors: Rieber Manuel , Castillo Miguel A.
Published: February 2007

Growth of B16 melanoma metastatic variants with 2.5 μg/ml of bromodeoxyuridine (BrdU) decreases cell detachment from the substratum, as measured by resistance to release by trypsin‐EDTA treatment. Using an antiserum to intact melanoma cells and metabolic labelling of melanoma metastatic variants with 3H‐glucosamine and subsequent electrophoretic analysis, we are now able to show that: (I) differential solubilization and immune precipitation permit the identification of hydrophilic glyco‐proteins of about 140 kD and 110 kD in melanoma cells with low colonizing ability; (2) the effects of BrdU on B16 melanoma appear to be exerted differentially on cells with differing metastatic behavior, since only poorly invasive melanoma cells show a stimulating effect of BrdU on the expression of the hydrophilic 140kD glycoproteins;(3) cells with increased lung colonizing ability reveal hydrophobic 140 and 110 kD glycoprotein species with increased susceptibility to mild protease treatment, as compared with the corresponding components from poorly invasive cells. The possible relationship of the 140–110 kD glycoproteins to B16 melanoma biological behavior and cell‐substratum interactions is suggested by the fact that such components undergo significant changes in cells with differing invasive behavior and detachment properties.
Transformation affects superoxide dismutase activity
Authors: Loven Dean P. , Guernsey Duane L. , Oberley Larry W.
Published: February 2007

A human, aging lung fibroblast cell strain manifested both copper‐zinc superoxide dismutase activity (CuZn‐SOD) and manganese‐containing superoxide dismutase activity (MnSOD), and these activities were found to be modulated by physiological concentrations of thyroid hormone. The immortal cell lines examined, whether normal or malignant, had no MnSOD activity. The immortal normal cell lines examined had CuZnSOD activity which was modulated by thyroid hormone, whereas the immortal malignant cell lines had CuZnSOD activity which was not affected, or not as strongly affected, by the presence of thyroid hormone.
A quantitative and qualitative study of the transglutaminase‐mediated insertion of polyamines into plasma proteins from patients with bronchopulmonary cancer
Authors: Roch Anne‐Marie , Thomas Vincent , Quash Gérard , Moulinoux Jacques Philippe , Delcros Jean Guy
Published: February 2007

The transglutaminase‐mediated incorporation of putrescine into proteins of plasma derived from 44 patients with histologically defined bronchopulmonary cancer was compared with that from an age‐matched group of 18 patients hospitalized with non‐malignant diseases. Two types of kinetic data were obtained over a range of putrescine concentrations 0.09 mM to 0.6 mM. Whereas the plasma from all the patients of the control group showed linear kinetics, that from only 24 patients of the cancer group showed linear kinetics. The remaining 20 showed kinetics typical of inhibition by excess substrate. PAGE analysis of [14C] putreascine‐bound plasma proteins showed around 15 different bands. Among these putrescine‐binding proteins, we identified, with the help of corresponding specific antisera, four protease inhibitors: alpha 2‐macroglobulin, alpha I‐antitrypsin, alpha I‐antichymotrypsin and antithrombin III.
Human T‐cell leukaemia virus (HTLV) in the United Kingdom
Authors: Greaves M. F. , Verbi W. , Tilley R. , Lister T. A. , Habeshaw J. , Guo H‐G. , Trainor C. D. , Robert‐Guroff M. , Blattner W. , Reitz M. , Gallo R. C.
Published: February 2007

Ten out of 26 leukaemic patients who had emigrated from the Caribbean region to the United Kingdom had adult T‐cell leukaemia with associated serum antibodies to HTLV I. Antibodies to HTLV were also detected in sera from a small proportion of non‐leukaemic Caribbean immigrants but not in any sera from other (non‐ATL) T‐cell leukaemias or a variety of control groups. The long period between immigration to the UK and diagnosis of leukaemia (up to 30 years) suggests that an extensive latent period in disease development may exist. Cell lines were isolated from two patients with HTLV antibody‐positive ATL and were shown to be virus‐positive by electron microscopy and immunofluorescence using antibodies to the p19 and p24 viral proteins. HTLV I provirus integration and active transcription were demonstrated by Southern blotting of DNA and in situ hybridization respectively using molecularly cloned HTLV I probes. Virus from one of these cell lines could be transmitted to normal T cells by co‐cultivation.
Expression of HLA‐DR antigens in nasopharyngeal carcinoma: An immunohistological analysis of the tumour cells and infiltrating lymphocytes
Authors: Thomas J. Alero , Iliescu Virginia , Crawford Dorothy H. , Ellouz Ridha , Cammoun Mohamed , De‐Thé Guy
Published: February 2007

A panel of conventional and monoclonal antibodies was used to examine the immunohistological characteristics of malignant epithelial cells and infiltrating lymphocytes in frozen sections of nasopharyngeal carcinoma (NPC) biopsies from 10 Tunisian patients. Three main categories of cells were identified. (1) Tumour cells which were positive for Epstein‐Barr nuclear antigen, HLA‐ABC and keratin determinants. In most samples, the tumour cells also expressed variable amounts of HLA‐DR antigens. The presence of HLA‐DR antigens has not been previously reported in NPC and may be a contributory factor in effecting the transfer of Epstein‐Barr virus to the epithelial cells. (2) Infiltrating lymphocytes which were mainly composed of T inducer (T4+) and T suppressor/cytotoxic (T8+) cells although one sample contained predominantly immature T cells expressing the HTA‐1+ cortical thymocyte phenotype. Few B cells or natural killer cells were demonstrated. (3) Large HTA‐1+ dendritic cells which were invariably present within the tumour masses. These were morphologically and phenotypically similar to antigen presenting Langerhans cells which are usually located in the skin but also found in other epithelial sites. These cells may be a residual population from the normal nasopharynx or represent part of a specific immunological response to the presence of Epstein‐Barr virus in the epithelial cells.
Proteinases and sialyltransferase in human breast tumors
Authors: Abecassis Joseph , Collard Régine , Eber Michel , Pusel Jean , Fricker Jean P. , Methlin GÉRard
Published: February 2007

Proteolytic and sialyltransferase activities were determined in extracts of 65 human primary breast tumors, 6 lymph node metastases, 6 fibroadenomas and 27 normal tissues. Using proteins and synthetic selective substrates, we observed the presence of collagen‐peptidases, plasminogen activator, cathepsin‐B and cathepsin‐D‐like enzymes, and sialyltransferase. No active or trypsin‐activatable type‐IV collagenase activity was detected. Although individual variations between tumors were large, proteinase and sialyltransferase contents were significantly elevated in malignant breast tissues. Enzyme activities were found to be related to the epithelial volume of the tumor. No significant correlation was found between the proteinase or sialyltransferase activities and the degree of differentiation of the tumor cells, or the degree to which tumors had metastasized to regional lymph nodes. Since large variations of enzyme levels apparently reflect the heterogeneity of epithelial cell densities in tumor samples, proteolytic or sialyltransferase activities cannot therefore be used as a measure of quantitative evaluation of invasive properties in breast cancer.
Target organ patterns of tumors in mice following the arterial dissemination of B16 melanoma cells
Authors: Weiss L. , Ward P. M. , Harlos J.‐P. , Holmes J. C.
Published: February 2007

The arrest of B16 melanoma cells and the subsequent development of tumors have been studied following left intraventricular injections (LVI) into mice of radiolabelled and unlabelled cells respectively; the proportions of cardiac output going to different target organs were also determined by LVI of radiolabelled microspheres. B16 cell arrest in the various target organs was as predicted by relative arterial blood supply, except in the lungs and liver where more radioactive counts were detected than could be accounted for in terms of initial arterial dissemination alone; and the numbers of counts remaining in all organs after 24 h were related to the numbers of counts initially obtained. When the incidence of tumor‐bearing organs was related to the cell arrest patterns, the organs could be divided into two major distinct groups. Within both of these groups, the patterns of tumor incidence were correlated with cancer cell delivery. These results on a model system suggest that the two major hypotheses used to account for metastatic patterns are not mutually exclusive: the “soil” effect divides the target organs into the two major groups; however, within these groups the incidence of tumors is explicable in terms of the “mechanical” hypothesis.
A fibrosarcoma model derived from mouse embryo cells: Growth properties and secretion of collagenase and metalloproteinase inhibitor (TIMP) by tumour cell lines
Authors: Hicks Nigel J. , Ward Robin V. , Reynolds John J.
Published: February 2007

A new murine fibrosarcoma model has been developed in which it is possible to compare in vitro the behaviour of tumour cells with that of normal parental cells from which the tumour was originally derived by spontaneous transformation in vitro. Tumour cell lines were obtained which showed differing capacities for localized invasion of the skin following subcutaneous injection: these were categorized as either highly invasive or poorly invasive and were compared with the normal cells for (1) their respective saturation densities when grown on plastic, (2) their ability to grow in agar, and (3) their secretions of the metalloenzyme collagenase and the specific inhibitor of metalloproteinases (TIMP). Although increased in vitro saturation density showed some correlation with increased invasiveness in vivo, the most striking correlation was the 10‐ to 20‐fold reduction in TIMP secretion by tumour cells of high invasive potential compared with normal cells or tumour cells with low invasive potential. No collagenase secretion by tumour cells was ever detected. It is proposed that local TIMP levels may play a crucial in the control of tumour invasion in vivo.
Regulation of mopc 104e by T cells and growth factors induced by C. Parvum stimulation
Authors: Shrestha K. , Hiramoto R. N. , Ghanta V. K.
Published: February 2007

Corynebacterium parvum, known for its ability to retard the growth of experimental neoplasms, was examined for its effect on the growth of murine plasmacytoma MOPC 104E in vivo and in vitro. Immunostimulation with C. parvum2 resulted in the accelerated growth of MOPC 104E in experimental animals, as measured by the tumor IgM production. The acceleration of plasmacytoma growth was seen in all cases where C. parvum was given before or at the time of tumor transplantation. Increased proliferation of MOPC 104E was also observed when MOPC 104E was co‐cultured in the presence of spleen cells from C. parvum stimulated mice as compared to the normal spleen cells. Removal of T cells by in vivo anti‐thymocyte serum treatment, followed by anti‐Thy 1.2 and complement in vitro, resulted in the partial loss of stimulatory activity. Furthermore, the stimulatory activity was shown to be associated with soluble mediators, which were generated by splenic adherent cells and T cells, and were, at least in part, responsible for the growth of plasmacytoma. Normal spleen cells did not generate a significant amount of soluble factor, but were able to augment MOPC 104E growth in co‐culture at high spleen to tumor cell ratio.
The impact of vaginal cytology on cervical cancer risks in cali, Colombia
Authors: Aristizabal Nubia , Cuello Carlos , Correa Pelayo , Collazos Tito , Haenszel William
Published: February 2007

The role of vaginal cytology screening in preventing invasive carcinoma of the cervix was investigated in Cali, Colombia. The history of previous participation in screening programs was obtained from 204 patients with invasive carcinoma and from 2 sets of age‐matched controls: one from the same health center and one for the same neighborhood of the patient. Our results show that the risk of developing invasive carcinoma is at least 10 times greater in non‐screened than in screened women.
Expression of laminin in thyroid gland and thyroid tumors: An immunohistologic study
Authors: Miettinen Markku , Virtanen Ismo
Published: February 2007

Thirty‐five thyroid tumors and four normal thyroids were immunohistochemically investigated for the presence of laminin, a major basement membrane component. The thyroid follicles in normal tissues and in nodular goiters were surrounded by a continuous rim of laminin positivity, as were also the papillae of papillary carcinomas. Follicular adenomas and well‐differentiated follicular carcinomas also showed laminin positivity around most of the follicles. Anaplastic thyroid carcinoma lacking a distinct compartmentalization of tumor cells also lacked pericellular laminin. However, in contrast to all other thyroid tumors, an intense laminin positivity was found in scattered tumor cells of anaplastic carcinomas. Laminin positivity is thus a feature reflecting the differentiation level of thyroid tumors, but, unlike most other carcinomas, differentiated thyroid tumors have basal laminae surrounding the differentiated structural units.
Interferon induction in human mixed leukocytetumor‐cell reactions: Evidence for restriction to a certain lineage expressing glycophorin A
Authors: Berger Rudolf , Knapp Walter , Kirchner Holger
Published: February 2007

This study reports the induction of interferon (IFN) in human mononuclear cells (MNC) by hematopoietic tumor cells. Only 3 out of 15 cell lines were capable of inducing IFN in the mixed leukocyte/tumor‐cell reaction (MLTR). K562, a pluripotent stem cell line and DUTKO‐1, a hybrid between K562 and Daudi (Burkitt lymphoma) induced high levels of antiviral activity (ranging from 50‐440 units IFN/ml). PUTKO‐I, a hybrid between K562 and P3HR‐1 (Burkitt lymphoma) induced very low levels of IFN (10 units/ml). This antiviral activity was produced by HLA‐DR+ adherent cells as revealed by different cell separation techniques, and shared well‐known properties of IFN γ (isoelectric point, inactivation by anti‐human IFN γ antibodies; species‐restricted protection). MLTR‐induced IFN induction could be blocked by enzyme treatment of tumor cells, but was still present when glutaraldehyde‐fixed cells were used for induction. Analysis of the cells by flow cytometry for expression of glycophorin A (GpA) revealed that expression of GpA correlated with the ability to induce antiviral activity in MLTR. Furthermore, isolated GpA could be used as a stimulant as well and the response to either K562 cells or soluble GpA was enhanced up to tenfold by the addition of a GpA‐specific monoclonal antibody.
A population‐based case‐control study of EBV and other viral antibodies among persons with Hodgkin's disease and their siblings
Authors: Evans Alfred S. , Gutensohn Nancy M.
Published: February 2007

The Epstein‐Barr virus (EBV) has been consistently found to be associated with Hodgkin's disease (HD) in two ways: cases generally have elevated titer distributions of antibodies against the viral capsid antigen, and the occurrence of HD among persons with a history of EBV infectious mononucleosis is two or three times higher than expected. We evaluated this association by measuring the prevalence and level of antibodies against EBV and related viruses among 304 cases of HD interviewed in a population‐based study in comparison to 285 of their siblings. The most significant finding was that antibody titers to the viral capsid antigen of EBV were elevated (± 1:320) in 39% of the cases and in only 14% of the sibling‐controls; the relative risk adjusted for age and sex was 4.1. The geometric mean titer was three‐fold higher among cases (175.6vs. 58.1) Subjects who reported a history of IM had a higher distribution of titers than those who did not. Cases also had elevated titers against the early antigen of EBV ‐ the D Component being most prominent. A significantly higher proportion of cases has elevated titers against CMV, relative risk = 3.4, but the prevalence of CMV antibody was relatively low and not consistently higher among cases. The findings support the hypothesis that EBV may play a role in the pathogenesis of HD among persons with elevated titers. The findings neither confirm nor deny a possible role of CMV.
Pregnancy in association with a newly diagnosed cancer: A population‐based epidemiologic assessment
Authors: Haas Joanna F.
Published: February 2007

Cancer patients who were pregnant at the time of cancer diagnosis were identified by the National Cancer Registry of the German Democratic Republic for the years 1970 through 1979. A total of 355 such cases occurred in women aged 15‐44, and during the same period 2,103,112 live births were registered. Rank by site in order of decreasing frequency was cervix, breast, ovary, lymphoma, melanoma, brain and leukemia. On the basis of general female population rates, 555.8 cases were expected, giving a significantly reduced observed to expected ratio (O/E) of 0.64. O/E ratios rose with age. The O/E for invasive carcinoma of the cervix was significantly elevated at 1.15; carcinoma in situ of the cervix occurred significantly less frequently than expected (O/E = 0.57). For breast, brain, melanoma and leukemia, significantly fewer cases were observed than expected. Explanations considered for the low number of pregnancy‐associated incident cancer cases include underreporting of pregnancy‐associated cancer, altered tumor progression in pregnancy or decreased fertility in women with early neoplastic disease.
Immune reactivity of the tumor‐resistant X/GF mouse
Authors: Nahas Fathallah , Segev Yardena , Gershon Harriet
Published: February 2007

Parameters of immune reactivity of the tumor‐resistant X/Gf mouse have been studied. X/Gf mice show better survival than do control strains following i.p. inoculation with graded doses of YAC lymphoma cells. The natural killer cell activity of X/Gf mice was higher than that of control mice, and this elevated NK activity was inherited by (C57BL/6 × X/Gf)F1 mice. Differences in NK activity of fresh spleen cells from X/Gf, C57BL/6, and (C57BL/6 × X/Gf)F1 mice were not reflected in their ability to lyse in vitro‐derived, cloned, transformed cell lines from X/Gf or C57BL/6 mice in an 8 h 51Cr assay; however, the X/Gf‐derived malignant cells were more sensitive to lysis than the C57BL/6‐derived cells. In order to test whether X/Gf mice demonstrated any exceptional ability to recognize and destroy altered autologous cells, experiments were performed with TNP‐modified syngeneic cells. While X/Gf and B10.A effector cells appeared to respond with similar magnitude, hapten‐modified X/Gf cells were stronger stimulator cells and more sensitive targets than control strain cells. The ability of X/Gf mice to reject H‐2 compatible and incompatible skin grafts is normal, as judged by a comparison of the rejection times with control strains. Allogeneic mixed lymphocyte reactivity, T‐cell‐mediated lympholysis, delayed‐type hypersensitivity reactions, and in vivo phagocytosis of inert particles are of comparable magnitude in X/Gf and control strain mice.