bluuebunny/crossref_metadata_2025 huggingface dataset:
Melanoma cell lysis by human CTL clones: Differential involvement of T3, T8 and HLA antigens
Authors: Fossati Giuseppe , Anichini Andrea , Parmiani Giorgio
Published: February 2007

Three lymphocyte clones, derived by micromanipulation from peripheral blood lymphocytes (PBL) of a melanoma patient and expressing a broad pattern of reactivity against different target cells, were analyzed for the involvement of T‐cell markers and HLA antigens in the lysis of target cells by blocking experiments with a panel of monoclonal antibodies (MAbs). The clones lysed autologous melanoma cells (Me 28) and 18 out of 22 allogeneic targets including neoplastic and normal cells of different histological origin. Anti‐T3 and anti‐T8 MAbs strongly inhibited the cytotoxicity of the lymphocyte clones against Me 28, 3 allogeneic melanomas and 3 carcinomas, but failed to affect the lysis of K562. Anti‐HLA class‐I MAb (w6/32) produced a significant enhancement of the lysis of Me 28 by the 3 clones without modifying cytotoxicity against one allogeneic melanoma or against K562 cells. Anti‐HLA class‐11 MAb (D1.12) did not affect the lysis of the same targets by the 3 clones. These results thus indicate that some anti‐melanoma CTL clones may interact with autologous tumor cells by the T3 and T8 structures in an HLA class‐1 unrestricted manner.
Cellular heterogeneity and drug resistance in two ovarian adenocarcinoma cell lines derived from a single patient
Authors: Wolf C. Roland , Hayward Ian P. , Lawrie Sandra S. , Buckton Karin , McIntyre Margaret A. , Adams David J. , Lewis Alexander D. , Scott Angela R. R. , Smyth John F.
Published: February 2007

Two ovarian cell lines were derived from the ascites of a patient before and after the onset of resistance to chemotherapy involving cis‐platinum, chlorambucil and 5‐fluorouracil. Characterization of these lines shows them to have various features in common and some significant differences. Cytologically the lines cannot be distinguished and they both contain high concentrations of oestrogen receptor. However, they do differ with respect to their growth characteristics, karyotype, glutathione content and sensitivity to cis‐platinum. The karyotypes of the 2 lines show several marker chromosomes in common but the resistant line contained a chromosome 8 and a 17 which were absent from the earlier sensitive line. This suggests a clonal origin with subsequent divergence to a heterogeneous population.
Hot beverages and oesophageal cancer in southern brazil: A case‐control study
Authors: Victora Cesar G. , Muñoz Nubia , Day Nicholas E. , Barcelos Lucio B. , Peccin Debora A. , Braga Noris M.
Published: February 2007

There is a cluster of high‐incidence areas of oesophageal cancer in south‐eastern South America, including Southern Brazil, Uruguay and parts of Argentina. The present case‐control study investigated the hypothesis that this may be due to the drinking of maté, a traditional beverage drunk at a very high temperature, and also studied the role of other known risk factors such as alcohol and tobacco. Cases (171) and age‐ and sex‐matched controls (342) were recruited from hospitals in the State of Rio Grande do Sul in Southern Brazil. The crude odds ratio for daily maté drinkers was 1.92 relative to those drinking less frequently than daily (p = 0.006). Other risk factors included the drinking of cachaça (a sugar cane spirit), smoking, rural residence, low fruit consumption and high intake of meats. After adjustment for these variables through conditional logistic regression, the odds ratio associated with daily maté drinking was reduced to 1.47 (90% CI = 0.87 ‐ 2.50). Although the study failed to provide evidence of a strong association between maté and oesophageal cancer, the cluster of high rates could be explained by relative risks of the magnitude observed. This is due to the fact that approximately 70% of adult males and 50% of females are daily drinkers. In addition, this study revealed that alcohol, tobacco smoking and rural residence are the main risk factors for oesophageal cancer in this population and the fruit consumption confers some degree of protection.
Immune control of SV40‐induced tumors in mice
Authors: Pan Sueihua , Abramczuk Jan , Knowles Barbara B.
Published: February 2007

The ability of mice to mount a cytotoxic T‐lymphocyte (CTL) immune response to SV40 T‐antigen is determined by the H‐2 haplotype of the host; H‐2b and k mice are high responders and H‐2d mice are low responders. Mice of these 3 H‐2 haplotypes were challenged with SV40 and their ability to generate and sustain an antibody response to SV40 T‐antigen was found to be equivalent. To investigate the role of the different components of the host immune response in controlling growth of SV40‐induced tumors, the tumorigenic potential of freshly established cell lines, obtained by SV40 transformation of cells from normal tissues of inbred strains of mice of 6 H‐2 haplotypes, was assessed. Each cell line was tumorigenic in athymic and newborn mice but not in adult syngeneic immunocompetent mice. Cells from these initial SV40‐transformed lines were then passaged in athymic (nu/nu) mice, re‐established in vitro and again transferred into syngeneic animals. Transfer of H‐2d SV40 transformants to low or non‐responder mice of the H‐2d haplotype resulted in tumor formation in some animals. Cells derived from these tumors expressed both the viral encoded T‐antigen and the H‐2Dd restriction element. Furthermore, the proportion of animals with tumors varied with the strength of their CTL‐responsiveness to SV40 T‐antigen in association with H‐2Dd. Therefore, in H‐2d animals, tumor cell growth appears to result from escape of cells from inefficient CTL surveillance. No tumors were formed by transfer of the in vivo selected H‐2b or H‐2k SV40 transformants to syngeneic high‐responder mice. We therefore investigated the role of CTL in the selection of SV40‐transformed cells able to escape immune surveillance. Under conditions of stringent immune selection by CTLs, tumorigenic cells that no longer expressed the relevant H‐2 class‐I restriction element were obtained. Although interaction between the various immune effector mechanisms may play a role in the recognition and elimination of SV40 transformants, our results were consistent with the hypothesis that the SV40‐specific CTL response is the predominant control of SV40 tumor growth.
Multiple epitope recognition: An approach to improved radioimmunodetection of tumor‐associated antigens
Authors: Giacomini Patrizio , Segatto Oreste , Natali Pier Giorgio
Published: February 2007

Three MAbs endowed with comparable affinity for 3 distinct epitopes of a HMW‐MAA have been employed to study whether the use of combinations of MAbs might improve the sensitivity of methods for the quantitation of TAAs both on the cell surface and in soluble form. To this end, different combinations and sequences of application of the 3 MAbs were used both in cell‐surface binding experiments and in solid‐phase radioimmunoassays. Results of this study show that only selected combinations of MAbs are capable of significantly improving the sensitivity of methods for HMW‐MAA detection, and that such improvements depend on the order and mode of addition of the 3 reagents. Thus, mixtures of MAbs to distinct epitopes carried by a single TAA molecule are likely to increase the sensitivity of tests for tumor detection both in vitro (i.e. radioimmunoassays) and in vivo (i.e. immunoscintigraphy). However, because the binding properties of such mixtures do not simply reflect those of the individual reagents, protocols for the use of MAb cocktails should be critically evaluated before clinical use.
Dna methylating activity in murine lymphoma cells xenogenized by triazene derivatives
Authors: Puccetti P. , Fuschiotti P. , Dominici P. , Borri‐Voltattorni C. , Romani L. , Fioretti M. C.
Published: February 2007

We investigated whether epigenetic rather than mutational events may be involved in the induction of novel immunogenicity (“xenogenization”) in murine lymphoma treated with triazene derivatives. To this end, we assessed the DNA methylation pattern of tumor cells during the course of in vivo or in vitro xenogenization by 2 triazenes, and compared it with the changes induced by the DNA hypomethylating agent 5‐azacytidine (5‐aza). While all of the tested agents were able to increase tumor cell immunogenicity, their effects on DNA methylating activity were opposite. In particular, the novel immunogenicity conferred by 5‐aza treatment correlated well with the extent of hypomethylation induced, whereas xenogenization by triazenes was accompanied by a limited increase in DNA methylating activity. Interestingly, the antimutagenic compound quinacrine, which is known to block the xenogenizing activity of triazenes, was incapable of hypermethylating effects, whereas the hypermethylating agent cytosine arabinoside (ara‐C) was apparently unable to interfere with the induction of novel immunogenicity by triazenes.
Ganglioside GM2 on the K562 cell line is recognized as a target structure by human natural killer cells
Authors: Ando Iwao , Hoon Dave S. B. , Suzuki Yasuo , Saxton Romaine E. , Golub Sidney H. , Irie Reiko F.
Published: February 2007

Although human NK cells lyse a wide spectrum of target cells, the precise target structure recognized by NK cells has not yet been elucidated. In order to define a possible relationship between gangliosides on human target cells and susceptibility to NK lysis, 14 human leukemia and lymphoma cell lines were studied. A significant correlation was observed between the quantity of ganglioside GM2 on the target cells and sensitivity to NK lysis. In a single‐cell binding assay purified GM2 specifically inhibited human NK cell binding to K562 target cells while other gangliosides did not inhibit binding. The competitive inhibition of NK cells by GM2 was restricted to the source of tissue from which GM2 was isolated. These results indicate that GM2 is a strong candidate as a target recognition structure for human NK cells.
Recombinant feline viruses containing the myc gene rapidly produce clonal tumours expressing T‐cell antigen receptor gene transcripts
Authors: Onions David , Lees Gillian , Forrest Douglas , Neil James
Published: February 2007

We, and others, have recently shown that recombinant feline leukaemia viruses (FeLV) containing the myc gene (FeLV‐myc) occur in up to 30% of naturally occurring cases of T‐cell lymphosarcoma. Investigation of the disease spectrum of two FeLV‐myc isolates showed that they induced clonal or oligoclonal T‐cell tumours after a short latent period. The pheno‐typic pattern of the thymic tumours was restricted in that they all expressed the alpha and beta chains of the T‐cell antigen receptor and could readily be established in culture in vitro without the addition of exogenous interleukin‐2. Although helper FeLV was transmitted from infected cats to uninfected tracer cats, there was no evidence of horizontal transmission of FeLV‐myc viruses, suggesting that these viruses arise de novo in individual cases of thymic lymphosarcoma.
Microscopic metastasis of a human lung carcinoma cell line in athymic nude mice: Isolation of a metastatic variant
Authors: Varki Nissi M. , Roome Leita , Sparkes Robert S. , Miller Jeffrey E.
Published: February 2007

A human lung carcinoma cell line, UCP3, was carried as subcutaneous xenotransplants in athymic mice. Autopsies of these animals showed rare foci of microscopically visible metastases in the lungs and lymph nodes. There were no metastases to any of the other organs. A metastatic variant, 522, was established serendipitously in vitro as a continuous cell line by blind isolation of the pulmonary metastatic foci, at the time of autopsy, from the lungs of the animals that carried subcutaneous xenotransplants of the parental cell line. The parental UCP3 and the metastatic variant 522 were examined by karyotypic and isoenzyme analysis and shown to be human and related. The metastatic variant, 522, metastasizes spontaneously from subcutaneous sites (like the parental UCP3). However, it forms larger subcutaneous xenotransplants and forms more metastatic foci in the lungs of the animals than does the parental cell line. Comparisons of the cell surface glycolipids show many similarities and a few differences. This model system may now be used for further investigations into the processes of metastasis of this human neoplasm.
Characterization of neural cell adhesion molecules (NCAM) expressed by ewing and neuroblastoma cell lines
Authors: Lipinski Marc , Hirsch Marie‐Rose , Deagostini‐Bazin Hermine , Yamada Osamu , Tursz Thomas , Goridis Christo
Published: February 2007

The status of the neural cell adhesion molecule NCAM gene which is mapped to human chromosome 11q23–24 has been investigated in Ewing‐tumor‐derived cell lines which present the t(11;22)(q23–24;q12) translocation characteristic of this malignancy. No rearrangement was detected when 2 different non‐overlapping probes to mouse NCAM were used. The expression of the NCAM gene was analysed at both the protein and messenger levels in material extracted from Ewing cell lines, human neuroblastoma cell line and fetal mouse brain. Immune blot and immunoprecipitation studies showed that the neuroblastoma cell line contained more NCAM material than the Ewing lines. In neuroblastoma but not in Ewing, the NCAM material had the electrophoretic characteristics of molecules with long polysialic acid chains. After treatment with endosialidase, the diffusely migrating neuroblastoma material was resolved into 3 discrete bands of 120, 140 and 180 kDa. In Ewing extract, high‐molecular‐weight NCAM species were also detected with a 3‐band pattern more reminiscent of mature brain. Endoglycosidase F treatment of Ewing NCAM indicated that all 3 species were largely N‐ glycosylated. Northern blot analysis confirmed that NCAM was expressed more abundantly in neuroblastoma than in Ewing cell lines. Among the 4 NCAM messengers (7.0, 6.5, 4.3 and 4.1 kb) detected in the neuroblastoma, the 6.5 kb species was largely predominant. The Ewing messenger RNA pattern was clearly different as the largest 7.0‐kb species was virtually absent and the other bands were of similar intensities.
A rat monoclonal antibody 4D7 produced by a hybridoma established from a yolk‐sac tumor‐bearing rat binds selectively to the stage‐specific embryonic antigen SSEA‐1
Authors: Lindvall Magnus L. , Brodin Thomas , Sjögren Hans Olov
Published: February 2007

A monoclonal rat IgM (kappa) antibody (MAb) is produced by a hybridoma obtained by fusion of the rat myeloma Y3 Ag 1.2.3 with spleen cells from a female W/Fu rat bearing a yolksac carcinoma isograft. In the rat this antibody (4D7) shows strong selective binding to all tested yolk‐sac carcinomas, but no binding to cultured cells of a number of other tumor types or to cells of normal tissues. Immunohistochemical analysis of the specificity of the antibody confirmed the strong binding to yolk‐sac carcinomas and also revealed binding to some other rat tissues. These include one colon carcinoma, the embryonic ectoderm and the primitive visceral endoderm of 8.5‐day‐old embryos, the central nervous system and the oviduct epithelium and some cells in the seminal tubules, the gastrointestinal epithelium and associated mucus and also the distal tubuli and collecting ducts of the kidney. The MAb binds strongly to purified SSEA‐1 but not to purified Lewis A glycolipid. It is concluded that the 4D7 MAb recognizes a determinant which is identical to or includes Galβ1–4(Fucα1–3) GlcNAc. The immunogenicity of the SSEA‐1 determinant is further confirmed by the demonstration that antibodies binding to purified SSEA‐1 but not to Lewis A appear in the sera of some of the rats developing primary yolk‐sac carcinoma.
Increased prevalence of human papillomaviruses in the lower genital tract of pregnant women
Authors: Schneider Achim , Hotz Marlies , Gissmann Lutz
Published: February 2007

In order to evaluate the influence of pregnancy on the presence of human papillomavirus (HPV) in the lower female genital tract, cervical smears of 92 pregnant and 96 non‐pregnant women, matched by age, were examined for the presence of HPV‐DNA by means of Southern blot hybridization. All patients had negative PAP smears. Twenty‐six (28%) of the pregnant women and 12 (12.5%) of the non‐pregnant women were positive for HPV. HPV 16 accounted for 42% of all positive pregnant cases and only 25% of the positive non‐pregnant cases. Smears of pregnant patients contained more than 10 pg viral DNA in 45% of the cases against 20% in the non‐pregnant group. HPV 16 showed the most active replication in both groups. This study demonstrates an increased prevalence of HPV (preferentially of HPV 16) and a higher replication rate of viral DNA during pregnancy.
Epidermal growth factor stimulates the synthesis of cell‐attachment proteins in the human breast cancer cell line PMC42
Authors: Thorne Heather J. , Jose David G. , Zhang Hui‐Ying , Dempsey Peter J. , Whitehead Robert H.
Published: February 2007

The human breast cancer cell line PMC42 responds to the addition of epidermal growth factor (EGF) by proliferation and increased frequency of attachment of cell‐organoid structures to the culture vessel. Antibodies to fibronectin and laminin reacted strongly, by immunoperoxidase, with the membranes of cells from organoids that became adherent following addition of EGF. This reaction was weak with membranes of cells of non‐adherent organoids in cultures containing EGF and was negative with membranes of cells of free‐floating organoids from cultures without EGF. An increase in biosynthetic labelling with 35S‐methionine was found in cell lysates and supernatants of PMC42 cells cultured in the presence of EGF compared with control cells grown without EGF. One‐dimensional SDS‐polyacrylamide gel electrophoresis and 2‐dimensional NEPHGE‐PAGE of labelled cell proteins showed increased synthesis of several cellular proteins and the appearance in EGF‐treated cells of 2 proteins which were not detected in cells from control cultures lacking EGF. Immunoprecipitation experiments using antibodies to fibronectin and laminin with lysates of 35S‐methionine labelled PMC42 cells cultured with EGF showed strong immunoprecipitation at Mr 200 and 400 with anti‐laminin, and at Mr 200 and 96 with antifibronectin. These immunoprecipitates were blocked specifically by purified laminin or fibronectin, respectively. No immunoprecipitates were detected with these antibodies in lysates from cells grown without EGF. EGF thus stimulates increased adherence of cultured PMC42 cell‐organoid structures together with increased membrane expression of the cell‐adhesive proteins laminin and fibronectin. These effects may play a role in normal development and neoplastic behaviour of breast epithelia.
Tumorigenioty of inorganic arsenic compounds following intratracheal instillations to the lungs of hamsters
Authors: Yamamoto A. , Hisanaga A. , Ishinishi N.
Published: February 2007

The tumorigenicity of arsenic trioxide (As2O3), calcium arsenate (Ca3(AsO4)2) and arsenic trisulfide (As2S3) was studied in male Syrian golden hamsters which received arsenic compounds containing a total dose of 3.75 mg arsenic by means of intratracheal instillations once a week for 15 weeks. As controls, some hamsters were treated with only the vehicle, phosphate buffer solution. During the animals' total life span, one lung adenocarcinoma was seen hi the 17 hamsters in the As2O3 group, one lung adenocarcinoma and 6 lung adenomas in the 25 hamsters in the Ca3(AsO4)2 group, one lung adenoma in the 22 hamsters in the As2S3 group and one lung adenosquamous carcinoma in the 21 hamsters in the control group. From these results, we conclude that calcium arsenate is tumorigenic to the lungs of Syrian golden hamsters. The results concerning the other 2 arsenic compounds were not conclusive.
Tumorigenicity of T24 urinary bladder carcinoma cell sublines
Authors: Flatow Ursula , Rabson Arnold B. , Rabson Alan S.
Published: February 2007

Two sublines of the T24 human urinary bladder carcinoma cell line which differ in tumorigenicity in nude mice have been studied (T24A and T24P). T24A obtained directly from the American Type Culture Collection is non‐tumorigenic while T24P obtained after multiple passages in several NCI laboratories produces tumors in 100% of inoculated mice. T24P cells differ morphologically from T24A, have a higher saturation density, are less serum‐dependent for growth, and are more sensitive to ouabain toxicity. Cytogenetic studies show that the 2 sublines differ significantly in chromosome number, with a modal chromosome range of 76–89 in T24A and a modal chromosome number of 48–51 in T24P. Southern blot analysis of Mspl cleaved T24A and T24P DNAs with the H‐ras Smal probe indicates that both contain only the activated mutant allele originally described in T24. Northern blot analysis shows equal amounts of the l.2kB ras polyadenylated message, and immunoblotting with rasHa antibody demonstrates no significant difference in the amounts of ras proteins. These results indicate that 2 sublines of a ras oncogene‐containing tumor cell line can differ greatly in tumorigenicity and other in vitro characteristics of transformation, and yet have similar expression of the ras oncogene. The fact that the tumorigenic cell line contains fewer chromosomes suggests that tumorigenicity may be related to the loss of some regulatory gene.
Expression of the c‐erbB‐2 protein in normal and transformed cells
Authors: Gullick William J. , Berger Mark S. , Bennett Paul L. P. , Rothbard Jonathan B. , Waterfield Michael D.
Published: February 2007

Two synthetic peptides from the predicted sequence of the human c‐erbB‐2 protein were synthesized and used to raise antisera in rabbits. The sequences chosen were identical to those in the homologous rat c‐neu protein. The antibodies produced reacted with the immunizing peptides in ELISA but showed little or no cross‐reaction with the partly homologous peptides found in equivalent positions in the human EGF receptor. Both antipeptide antibodies, and a monoclonal antibody (MAb) specific for the rat new protein, immuno‐precipitated a 185‐kDa protein from 35S‐methionine‐labelled lysates prepared from a rat cell line known to express high levels of the c‐neu protein. The antipeptide antibodies also recognized a protein of the same size in Western blots. In addition, both antipeptide antibodies immunoprecipitated a 190‐kDa protein from labelled cell lysates prepared from human and monkey cells. Antibodies to one of the peptides, which showed no detectable cross‐reaction with human, rat or monkey EGF receptor, were used to examine the expression of the c‐erbB‐2 protein on a variety of cultured cell types. Eleven transformed, I non‐established and 2 immortalized cell types were examined by immunoprecipitation for their level of expression of the c‐erbB‐2 protein and of the EGF receptor. The numbers of EGF receptors varied widely between different cell lines, whereas the level of the c‐erbB‐2 protein, which was found on all of the cell types examined, was more constant. The number of c‐erbB‐2 molecules present was estimated by autoradiography to be about 100,000 per cell. The antibodies were then used to examine the location and level of expression of the human c‐erbB‐2 and rat c‐neu proteins in normal tissues. Immunohistochemical staining showed that the c‐erbB‐2 protein was highly expressed in rat kidney proximal tubules and loop of Henle. The c‐enbB‐2 protein was also present on normal human epithelial cells but in some cases with a different distribution to that of the EGF receptor.
Establishment and characterization of a human IgA‐κ‐secreting plasma cell line (MT3)
Authors: Donelli Amedea , Narni Franco , Tabilio Antonio , Emilia Giovanni , Selleri Licia , Colo Alessandro , Zucchini Patrizia , Montagnani Giuliano , Torelli Giuseppe , Torelli Umberto
Published: February 2007

We have established a new human plasma cell line from the peripheral blood of a patient with an IgA‐k plasma‐cell leukemia. Morphological, immunological, cytogenetic and molecular studies confirm that the cultured cells are derived from the same clone of leukemic plasma cell in vivo. The established cell line (MT3) grows in suspension, secretes high amounts of IgA k and exhibits morphological and ultrastructural characteristics of plasma cells. Surface marker analysis shows that both primary and cultured cells express the plasmacell‐associated antigens PCA‐1 and T10, while specific B‐and T‐cell determinants and EBV nuclear antigen are undetectable. In the established cell line a few cells express la‐like and CALLA antigens. Cytogenetic analysis of MT3 cells reveals a prevalent hypertriploid karyotype with constant chromosomal aberrations consisting of 14q + 22q‐and marker chromosomes.
Spontaneous mutation rates in cloned murine tumors do not correlate with metastatic potential, whereas the prevalence of karyotypic abnormalities in the parental tumors does
Authors: Kendal Wayne S. , Wang Rui‐Yu , Frost Philip
Published: February 2007

We tested the hypothesis that highly malignant cell lines are genomically more unstable than their less malignant counterparts, and that this instability is more pronounced in clones than in cell lines. We compared MDAY‐D2 to its non‐metastatic variant, D36W25, with regard to (I) the rate of development of ouabain resistance within parallel clones and (2) the prevalence of G‐banded karyotypic abnormalities. We detected no significant difference between the spontaneous mutation rates for ouabain resistance. However, the MDAY‐D2 cell line possessed both a higher prevalence and greater diversity of chromosomal abnormalities. One possible explanation for these seemingly inconsistent results is that genomic instability may remain essentially constant throughout tumor progression, whereas an accumulation of genetic changes may be responsible for the observed increased prevalence of abnormalities and the development of selective survival advantages during progression.
Chemotherapy with estrogenic recruitment and surgery in locally advanced breast cancer: Clinical and cytokinetic results
Authors: Conte P F , Alama A. , Bertelli G. , Canavese G. , Carnino F , Catturich A. , Marco E Di , Gardin G. , Jacomuzzi A. , Monzeglio C. , Mossetti C. , Nicolin A. , Pronzato P. , Rosso R.
Published: February 2007

Thirty‐nine patients with locally advanced breast cancer (T3b‐4, N13 or inflammatory carcinoma) received 3 cycles of induction chemotherapy with estrogenic recruitment before surgery. The therapeutic regimen consisted of diethylstilbestrol (DES) orally on days 1–3, 5‐Fluorouracil + Doxorubicin + Cyclophosphamide on day 4 q 21 days (DES‐FAC). After surgery 6 additional cycles of chemotherapy (3 DES‐FAC alternating with 3 DES‐CMF with Methotrexate + F and C as in FAC) were administered. The objective response rate was 71.11% with 15.4% CR, and 56.4% PR; after surgery 36/39 (92 3%) patients were rendered disease‐free. So far, 13 of 26 patients in stage 111b have relapsed (9 of 13 with inflammatory carcinomas). Three‐year survival and progression‐free survival are 60% and 53.5%, respectively. Twenty‐three of the 39 patients were subjected to serial tumor biopsies during the first DES‐FAC regimen to allow for tumor‐cell kinetic studies during DES and chemotherapy. A significant estrogenic recruitment occurred in 16 patients (69.6%), irrespective of estrogen‐receptor status. At surgery, 3–4 weeks after induction chemotherapy, tumor proliferate activity was significantly depressed in comparison to basal values. These results indicate that breast cancer cells can be recruited in vivo with DES and that chemotherapy following estrogenic stimulation is effective and feasible with acceptable toxicity.
A cell line from Wilms' tumour with deletion in short arm of chromosome 11
Authors: Kumar S. , Harrison Christine J. , Heighway J. , Marsden H. B. , West D. C. , Jones Pat Morris
Published: February 2007

A cell line (T3/73) from a Wilms' tumour has been established from a 9‐month‐old boy with aniridia. The tumour was removed in 1973. On histological examination a diagnosis of Wilms' tumour was made which showed undifferentiated areas, marked tubule formation and abundant striped muscle fibers. The tumour cells, which are fusiform, grew rapidly in culture without the addition of growth factors, and have undergone over 100 passages. Approximately 95% and 5% were positive for desmin and cytokeratin, respectively. The cell doubling time was 28 hr. Cytogenetic studies revealed a karyotype of 46, XY, del(11) (p12::p14). Although the cells stained very intensely with a monoclonal antibody that detects oncogene ras p 21 antigen, Southern blot analysis using c‐Ha‐ras as a probe failed to reveal an obvious deletion or amplification of either Ha‐ras allele.
Regulation of cell‐surface receptors for hematopoietic differentiation‐inducing protein MGI‐2 on normal and leukemic myeloid cells
Authors: Lotem Joseph , Sachs Leo
Published: February 2007

The normal myeloid hematopoietic regulatory proteins include 4 different growth‐inducing proteins (IL‐3, MGI‐1GM = GM‐CSF, MGI‐1G = G‐CSF, and MGI‐1M = M‐CSF = CSF‐1). There is also another type of normal myeloid regulatory protein (MGI‐2) with no MGI‐1 (CSF or IL‐3) activity, which can induce differentiation of normal myeloid precursors and certain clones of myeloid leukemic cells. Studies on the binding of MGI‐2 to differentiation‐competent (D+) and differentiation‐defective (D−) clones of mouse myeloid leukemic cells and to normal cells indicate that: (1) D+ clones of myeloid leukemic cells had about 2,500 high‐affinity surface receptors per cell, like mature normal myeloid cells, and the bound MGI‐2 was rapidly internalized with its cell‐surface receptors at 37°C causing down‐regulation of MGI‐2 receptors in both the normal and leukemic cells; (2) in some D− clones, the number and internalization of MGI‐2 receptors were similar to those of D+ clones whereas other D− clones had only 0–100 MGI‐2 receptors per cell; (3) normal thymus and lymph‐node lymphocytes and T lymphoma cells did not show detectable MGI‐2 receptors; (4) there was an independent expression of receptors for MGI‐2 and for the 4 myeloid growth‐inducing proteins on different clones of myeloid leukemic cells; and (5) none of the 4 myeloid growth‐inducing proteins IL‐3, MGI‐1GM, MGI‐1G, or MGI‐1M, inhibited binding of MGI‐2 to its receptors. The cytotoxic proteins lymphotoxin and tumor necrosis factor did not induce differentiation of the mouse myeloid leukemic cells and also did not inhibit binding of MGI‐2 to its receptors. These results show that the myeloid differentiation‐inducing protein MGI‐2 binds to cell‐surface receptors that are different from the receptors for the 4 myeloid growth‐inducing proteins and these cytotoxic proteins.
Lung cancer among Chinese women
Authors: Gao Yu‐Tang , Blot William J. , Zheng Wei , Ersnow Abby G. , Hsu Cheng Wen , Levin Lynn I. , Zhang Rong , Fraumeni Joseph F.
Published: February 2007

A case‐control stud/involving interviews with 672 female lung cancer patients and 735 population‐based controls was conducted to investigate the high rates of lung cancer, notably adenocarcinoma, among women in Shanghai. Cigarette smok‐ ing was a strong risk factor, but accounted for only about one‐ fourth of all newly diagnosed cases of lung cancer. Most patients, particularly with adenocarcinoma, were life‐long non‐smokers. The risks of lung cancer were higher among women reporting tuberculosis and other pre‐existing lung diseases. Hormonal factors were suggested by an increased risk associated with late menopause and by a gradient in the risk of adenocarcinoma with decreasing menstrual cycle length, with a 3‐fold excess among women who had shorter cycles. Perhaps most intriguing were associations found between lung cancer and measures of exposure to cooking oil vapors. Risks increased with the numbers of meals cooked by either stir frying, deep frying or boiling; with the frequency of smokiness during cooking; and with the frequency of eye irritation during cooking. Use of rapeseed oil, whose volatiles following high‐temperature cooking may be mutagenic, was also re‐ ported more often by the cancer patients. The findings thus confirm that factors other than smoking are responsible for the high risk of lung cancer among Chinese women and provide clues for further research, including the assessment of cooking practices.
An estimate of the proportion of colo‐rectal and stomach cancers which might be prevented by certain changes in dietary habits
Authors: Wahrendorf Jürgen
Published: February 2007

The Colo‐rectum and stomach are the 2 sites for which the role of diet in the etiology of cancer is most heavily implicated. Quantitative estimates as to the proportion of cancer deaths attributable to diet vary considerably. This may be partially due to the application of the concept of population attributable risk which has proved a useful yardstick in estimating the public health impact of completely removing an exposure factor under study. This simple concept may well serve in occupational epidemiology, but with more and more risk factors found on a metric scale, or at least characterized on an ordinal scale, extensions should be considered. In this report, a preventable proportion is defined as the excess risk which would be removed if the population exposure distribution were to change in a favorable direction. A simple way of modelling such changes is proposed. This new measure is illustrated with data from 6 case‐control studies on cote‐rectal or stomach cancer. The results Indicate that the proportion of these cancers which may be prevented assuming arbitrary shifts of a single risk factor towards the next lower risk category if populations were to change their dietary habits is in the order of magnitude of 15% to 20%. This figure is much lower, but not necessarily in contradiction to the figures considered for the proportion of cancers attributable to diet.
Characterization of actinomycin‐D‐resistant CHO cell lines exhibiting a multidrug‐resistance phenotype and amplified DNA sequences
Authors: Diddens Heyke , Gekeler Volker , Neumann Manfred , Niethammer Dietrich
Published: February 2007

Actinomycin D (DACT)‐resistant sublines of the Chinese hamster ovary cell line CHO‐K, were selected in vitro. Sublines were derived which expressed 5.2‐fold (CHO 15DACT) and 35.8‐fold (CHO 100DACT) resistance to DACT. The CHO 100DACT subline displayed marked cross‐resistance to bleomycin, adriamycin, daunomycin, vinblastine, vincristine, VP 16 and VM 26. No cross‐resistance was found to cisplatin or methotrexate. The resistant cells exhibited enhanced (collateral) sensitivity to prednisolone. Combination of prednisolone with vincristine resulted in a pronounced synergistic effect on sensitive cells, whereas in resistant cells the combined effect of both drugs was merely additive. Resistant cells, viably stained with the DNA‐specific dye Hoechst 33342, exhibited decreased fluorescence intensities compared to parental cells. In contrast to sensitive cells the resistant sublines did not accumulate the mitochondria‐specific dye rhodamine 123. Co‐incubation with verapamil, however, effectively enhanced accumulation of the dye. The potential diagnostic value of these fluorescent compounds as marker dyes for the multidrug‐ resistance phenotype is discussed. Non‐toxic doses of verapamil almost completely reversed the resistance to various drugs in CHO 100DACT cells. Specific DNA sequences were amplified in resistant cells, and the increase in resistance was paralleled by a concomitant increase in the copy number of these sequences, suggesting that the corresponding gene may be I functionally linked to the multidrug‐resistance phenotype.
Simultaneous production of IGF‐I and EGF competing growth factors by HT‐29 human colon cancer line
Authors: Culouscou Jean‐Michel , Remacle‐Bonnet Maryse , Garrouste Françoise , Marvaldi Jacques , Pommier Gilbert
Published: February 2007

The conditioned medium from the HT‐29 human colonic adenocarcinoma cell line contains a potent mitogenic activity that can markedly stimulate the proliferation of both rat and human fibroblasts in the absence of serum. Fractionation of conditioned medium on Bio‐Gel P‐100 shows that HT‐29 cells simultaneously produce 2 different types of endogenous growth factors. The first one (molecular mass of 35,8 and 5.5 kDa) exhibits an IGF‐I competing activity which is positively correlated to mitogenic activity. This mitogen is recognized by anti‐IGF‐1 antibodies but Is resistant to reducing agents. It is distinct from IGF‐II, insulin and PDGF. The second one (molecular mass of 40‐and 20‐kDa) is able to displace EGF binding to its receptor. This factor is immunologically recognized by anti‐EGF antibodies but with a lower affinity as compared to EGF. This suggests that this endogenous HT‐29‐growth factor is related to but distinct from native EGF. Although more active in radioreceptor assay than in radioimmunoassay, the EGF‐competing factor is distinct from TGF α or β since it is unable to induce anchorage‐independent growth of NRK or FR3T3 target cells in the presence or absence of exogenous EGF. Moreover, free functional EGF receptors are available at the HT‐29 cell surface.
Invasiveness, proliferative activity and ultrastructural phenotypes of hepatocytes from diethylnitrosamine‐induced neoplastic nodules and hepacarcinomas in vitro
Authors: De Ridder L. , Mosselmans R. , Bernaert D. , Galand P.
Published: February 2007

The invasive behavior of hepatocytes from diethylnitrosamine (DENA) induced neoplastic nodules and hepatocarcinomas was studied in a confronting culture system in vitro. These observations confirm our previous report, demonstrating that hepatocytes from hepatocarcinomas and from neoplastic nodules invaded into embryonic chick precultured heart fragments (PHF), a property associated with malignancy (Mareel, 1979). We now further demonstrate that: (1) Invasiveness was expressed by the hepatocytes in 10 out of 12 samples from hepatocarcinomas, and in 13 out of 36 confronted nodular samples. The hepatocytes from the other two‐thirds of nodule samples died off in the confrontation as did all normal hepatocytes. (2) Invasive hepatocytes from tumors and from nodules showed the same arrangement of invasive liver cells in relation to the heart tissue, and the same ultrastructural phenotypes. The latter did not differ from those in the non‐invading subpopulations, with the exception perhaps of a higher proportion of cells with an indented nucleus. (3) None of the scored ultrastructural alterations was present in all the invasive cells, thus excluding any specific requisite in this respect. (4) When 3H‐TdR was made continuously available to the cultures, starting at the time of confrontation between heart and liver tissues, unlabelled as well as labelled invasive hepatocytes were found inside the PHF in about equal proportions. It is concluded that nodular hepatocytes deviate from normality by at least 2 different properties that may or may not be related to each other and are revealed under in vitro conditions, namely the ability to survive and to proceed through S‐phase and mitosis under such conditions and to actively invade precultured chick heart fragments. The latter property indicates that at least some of the nodules contain hepatocytes that have performed one step in malignant progression.
Stimulation by EGF of the growth of EGF receptor‐hyperproducing tumor cells in athymic mice
Authors: Ozawa Soji , Ueda Masakazu , Ando Nobutoshi , Abe Osahiko , Hirai Masamichi , Shimizu Nobuyoshi
Published: February 2007

EGF receptor‐hyperproducing cells of squamous carcinoma origin were inoculated s.c. into the bilatero‐abdominal regions of athymic mice and a mini‐osmotic pump containing EGF was implanted on the back. After 2 weeks the tumors formed from 5 different cell lines in the presence of EGF weighed 3 to 6 times more than those formed in the absence of EGF. The cells recovered from these tumors maintained their original characteristics such as the amplified EGF receptor gene, high numbers of EGF receptors and a sensitivity to EGF‐mediated inhibition of growth in vitro. These results suggest that EGF plays an important role in promoting growth of squamous‐cell carcinoma in vivo.
Analysis of the chromosomal abnormalities of a woodchuck hepatocellular carcinoma‐derived cell line (WH257GE10)
Authors: Matsushita Fumiaki , Ohno Shinsuke , Unoura Masashi , Kobayashi Kenichi , Tanaka Nobuyoshi , Fukuoka Kenichi , Morioka Takeshi , Kaneko Shuichi , Aoyama Syou , Migita Shunsuke , Hattori Nobu
Published: February 2007

The normal woodchuck karyotype was determined by the G‐banding technique, and the chromosomal abnormalities of a woodchuck hepatocellular carcinoma‐derived cell line (WH257GE10) were analyzed and compared with it. The normal woodchuck karyotype was 38, XY in a male, and 38, XX in a female. Autosomes were classified into 2 groups (A and B). Group A consisted of 13 pairs (1–13) of metacentric or submetacentric chromosomes, and group B consisted of 5 pairs (14–18) of telocentric or sub‐telocentric ones. The X chromosome was sub‐metacentric, and the Y chromosome was telocentric. In WH257GE10, the modal number was 36. Deletion of one of the chromosome 5 pair, of the chromosome 13 pair, and of the Y chromosome was observed. Two marker chromosomes (M1and M2) were found. These markers showed the same G‐banded patterns except for a small chromosome fragment at the distal part of the long arm of M1. The chromosome aberrations were very stable through successive passagesin vitro.These findings suggest that the chromosomal abnormalities found in WH257GE10 might be associated with the pathogenesis of woodchuck hepatocellular carcinoma.
Epidemiological features of HTLV‐I carriers and incidence of ATL in an ATL‐endemic island: A report of the community‐based co‐operative study in Tsushima, Japan
Authors: Tajima Kazuo , Kamura Sueo , Ito Shin‐Ichiro , Ito Mizuko , Nagatomo Masazumi , Kinoshita Ken‐Ichiro , Ikeda Shuichi
Published: February 2007

To extend the epidemiological study on adult T‐cell leukemia‐lymphoma (ATL) in japan, the geographical and demographic characteristics of carriers of human T‐lymphotropic virus type I (HTLV‐I) and patients with ATL were analyzed in Tsushima Island, which is one of the typical endemic areas of ATL in Kyushu, japan. Even on the small island of Tsushima (710 km2; pop. 48,875; 123 villages), the positive rates of anti‐HTLV‐1 antibody among the 58 villages studied varied from 2% to 50%, a fact that is probably associated with the historical events affecting the movement of the indigenous population of Tsushima Island. The positive rate of anti‐HTLV‐1 antibody in males increased little with age; however, the female rate increased distinctly with age in moderate and high HTLV‐1‐endemic villages where more than 15% of the inhabitants had positive anti‐HTLV‐1 antibody. Analysis of anti‐HTLV‐1 antibody positivity between spouses confirmed that HTLV‐1 was more contagious from husband to wife than from wife to husband, which corresponded to the fact that the positive rate of anti‐HTLV‐1 antibody in females older than 30 years was higher than that in males. Recently the rate of carrier children from HTLV‐1 carrier mothers was estimated at around 20%. The recent annual incidence rates of ATL among 1,000 HTLV‐1 carriers older than 40 years living in Tsushima Island was estimated at 2.2 in males, 0.8 in females.
Antibody‐antigen complex formation following injection of OC125 monoclonal antibody in patients with ovarian cancer
Authors: Haisma Hidde J. , Battaile Anne , Stradtman Earl W. , Knapp Robert C. , Zurawski Vincent R.
Published: February 2007

Monoclonal antibody (MAb) OC125 binds to approximately 80% of epithelial ovarian cancers. Serum antigen, CA125, can be detected in these patients. 1311‐OC125‐F(ab)2 was injected into 5 ovarian carcinoma patients with preinjection serum levels of 150 to 9,000 CA125 U/ml. Patients received the antibody intravenously in doses ranging from 0.46 to 0.94 mg with a specific activity of approximately 2.5 mCi/mg 1311. The half‐ life in the circulation was approximately 30 hr and was independent of serum CA125 levels. Clearance of 1311 from the circulation fitted an open, one‐compartment mathematical model. Gel filtration chromatography revealed antibody‐antigen complexes in sera 15 min after injection of the radiola‐belled antibody. By 5 days after injection, the free form of OC 125 antibody could not be detected in the serum. The rate of complex formation correlated well with the observed preinjection serum CA125 levels. This direct correlation was verified in vitro using purified CA125 antigen and radiola‐beled OC125 F(ab)2 fragments. The specific effects of complex formation on tumor localization remains unclear. However, the presence of complexes should not be ignored, when planning for diagnostic imaging or immunotherapy with OC 125 or other MAbs reacting with circulating antigen.
Absence of the hybrid bcr‐abl mRNA in Ph1‐positive B lymphoblastoid cell lines established from a patient with chronic myelogenous leukemia
Authors: Yamada Toshiyuki , Oikawa Tsuneyuki , Kuzumaki Noboru , Takagi Nobuo , Sasaki Motomichi
Published: February 2007

The expression of c‐abl, c‐sis, c‐myc and N‐ras oncogenes was examined in 2 lymphoblastoid cell lines, one with Ph1 (PB‐1049) and the other without Ph1 (LN‐1049), both established from a patient with chronic myelogenous leukemia (CML), and in a Ph1‐positive cell line (PB‐1049‐T) derived from a tumor formed after transplantation of PB‐1049 cells in a nude mouse with reference to their tumorigenic potential in nude mice. The normal transcripts of c‐abl were detected in all 3 lymphoblastoid cell lines. Although in situ hybridization of v‐abl proved, and restriction endonuclease analyses of the bcr region strongly indicated the occurrence of bcr‐abl rearrangement in PB‐1049 and PB‐1049‐T, we could not obtain any evidence for the expression of the hybrid bcr‐abl mRNA. These results indicate that the Ph1 translocation does not ensure the production of the hybrid bcr‐abl mRNA, and that the expression of hybrid bcr‐abl gene is not essential for the maintenance of tumorigenicity of these cell lines. Expression of c‐sis was not detected in any of the cell lines examined, whereas the expression of c‐myc was uniformly higher in the 3 cell lines than in normal control cells. The levels of N‐ras expression varied considerably, probably in parallel with the changes in tumorigenicity of the cell lines. N‐ras expression in the PB‐1049 and PB‐1049‐T cell lines was higher than that in the LN‐1049 line when they retained tumorigenic potential, but it fell to the level of LN‐1049 with loss or decline of tumorigenicity.
Carcinogenicity of diethylnitrosamine in vitamin‐A‐deficient mice
Authors: Santhanam Uma , Lautha V. S. , Bhide S. V.
Published: February 2007

The effect of suboptimal levels of dietary vitamin A on diethylnitrosamine (DEN) carcinogenesis was studied in BALB/c and Swiss mice. Two different dietary regimens were employed to induce vitamin A deficiency and DEN was administered by gavage at 2 dose levels: 0.6 mg/kg as a single dose and 200 mg/kg in 4 divided doses. Shark liver oil (SLO) which was the main source of vitamin A in the standard diet, was deleted in one regimen and reduced to 25% in the other. The mice maintained on the former diet were given a high dose of DEN and those on the latter diet received a low dose. In both strains the deficient mice had a greater tumour incidence than those on standard diet with a marginal reduction in the latent period. At the low level of DEN there was shift in organotrophy, i.e. from liver in controls to lung in the vitamin‐A‐deficient mice of BALB/c strain. With the higher dose, lung adenomas predominated in deficient as well as control groups in both the strains. Forestomach carcinomas appeared in deficient mice and not in the controls.