bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiation dose and breast cancer risk in patients treated for cancer of the cervix
Authors: Boice John D. , Blettner Maria , Kleinerman Ruth A. , Engholm Göran , Stovall Marilyn , Lisco Hermann , Austin Donald F. , Bosch Antonio , Harlan Linda , Krementz Edward T. , Latourette Howard B. , Merrill James A. , Peters Lester J. , Schulz Milford D. , Wactawski Jean , Storm Hans H. , Björkholm Elisabet , Pettersson Folke , Bell Cm. Janine , Coleman Michel P. , Fraser Patricia , Neal Frank E. , Prior Patricia , Won Choi N. , Hislop T. Gregory , Koch Maria , Kreiger Nancy , Robb Dorothy , Robson Diane , Thomson D. H. , Lochmüller H. , Fournier Dietrich Von , Frischkorn Rolf , Kjørstad Kjell E. , Rimpelä Arja , Pejovic Marie‐Héléne , Kirn Vera Pompe , Stankusova Hanna , Pisani Paola , Sigurdsson Kristjan , Hutchison George B. , Macmahon Brian
Published: February 2007

The relationship between breast cancer and radiation treatment for cervical cancer was evaluated in an international study of 953 women who subsequently developed breast cancer and 1,806 matched controls. Radiation doses to the breast (average 0.31 Gy) and ovaries (average 32 Gy) were reconstructed for exposed subjects on the basis of their original radiotherapy records. Overall, 88% of the breast cancer cases and 89% of the controls received radiation treatment [relative risk (RR) = 0.88; 95% confidence interval (CI) = 0.7‐1.2]. Among women with intact ovaries (561 cases, 1,037 controls), radiotherapy was linked to a significant 35% reduction in breast cancer risk, attributable in all likelihood to the cessation of ovarian function. Ovarian doses of 6 Gy were sufficient to reduce breast cancer risk but larger doses did not reduce risk further. This saturation‐type response is probably due to the killing of a critical number of ovarian cells. Cervical cancer patients without ovaries (145 cases, 284 controls) were analyzed separately because such women are at especially low natural risk for breast cancer development. In theory, any effect of low‐dose breast exposure, received incidentally during treatment for cervical cancer, should be more readily detectable. Among women without ovaries, there was a slight increase in breast cancer risk (RR = 1.07; 95% CI = 0.6‐2.0), and a suggestion of a dose response with the RR being 1.0, 0.7, 1.5 and 3.1 for breast doses of 0,0.01‐0.24, 0.25‐0.49 and 0.50 + Gy, respectively. However, this trend of increasing RR was not statistically significant, if low‐dose radiation increases the risk of breast cancer among women over age 40 years, it appears that the risk is much lower than would be predicted from studies of younger women exposed to higher doses.
Height and weight in relation to breast cancer morbidity and mortality. A prospective study of 570,000 women in Norway
Authors: Tretli Steinar
Published: February 2007

The height and weight of 570,000 Norwegian women, aged 30‐69 years, were measured and the subjects were then followed up for 6‐18 years with regard to breast cancer morbidity and mortality. They were arranged in 5‐year age‐groups. In all age‐groups the tallest women were found to have the highest risk for both morbidity and mortality. Overweight was a risk factor for breast cancer mortality in all age‐groups, but it was a risk factor only in the post‐menopausal age‐groups in the case of morbidity. It appeared to protect against breast cancer in the pre‐menopausal age‐group. Stages I and II—IV follow‐up endpoints show negative and positive associations, respectively, with overweight. It is not likely that this can be fully explained by earlier detection of cancer among slim women.
Patterns of migration indicate sexual transmission of HTLV‐I infection in non‐pregnant women in papua new guinea
Authors: Brabin L. , Brabin B. J. , Doherty R. R. , Gust I. D. , Alpers M. P. , Fujino R. , Imai Joko , Hinuma Y.
Published: February 2007

The prevalence of infection with human T‐cell leukaemia virus (HTLV‐I) was studied in Madang Province on the north coast of Papua New Guinea. Serum specimens collected from non‐pregnant women in 17 villages were tested for anti‐HTLV‐I by gelatin particle agglutination screening and confirmed by immunofluorescence and Western blotting. Overall, 13.9% of subjects were antibody‐positive, with the prevalence of antibodies varying from <10% to 30% in villages situated less than 10 km apart. Two groups of migrant women were identified, and in both a parity‐related increase in antibody prevalence which occurred only after marriage suggested that the predominant mode of transmission in migrant women was sexual. There was no parity‐associated increase in anti‐HTLV‐l in indigenous women, and in contrast to migrant women, nulliparous indigenous women had a high prevalence of antibody (16.8% vs. 0%; p = 0.005). Vertical transmission cannot be excluded in indigenous women. No correlation was detected between the prevalence of anti‐HTLV‐l and a variety of indices of malarial infection.
Nation‐wide study of lethal mid‐line granuloma in Japan: Frequencies of Wegener's granulomatosis, polymorphic reticulosis, malignant lymphoma and other related conditions
Authors: Aozasa Katsuyuki , Ohsawa Masahiko , Tajima Kazuo , Sasaki Ryoji , Maeda Hajime , Matsunaga Torn , Friedmann I.
Published: February 2007

Lethal mid‐line granuloma (LMG) is a clinical term, and it is histologically composed of Wegener's granulomatosis (WG), polymorphic reticulosis (PR), and malignant lymphoma (ML). WG is an inflammatory disease, and PR and ML are considered to represent a neoplastic proliferation of lymphoreticu‐lar cells. In the present report, a nation‐wide study on LMG in Japan is compared with a study from the UK, to examine differences in frequencies of each disease in Eastern and Western countries. A total of 340 cases of LMG were examined. On the basis of histological and clinical findings, these cases were categorized as 68 WG, 129 PR, 92 ML, 44 chronic inflammation not specified, and 7 other related conditions. The crude frequencies of WG, PR, and ML per 100,000 outpatients of ENT clinics in Japan and England were 4, 8 and 6, respectively and 8, 4 and 1, respectively. The predominance of malignant lym‐phoproliferative diseases to WG in Japan (3.5:P was in marked contrast to the situation in the UK (1: 1.6). A. eview of the pertinent literature suggests a clustering of malignant lymphoproliferative diseases of the nose among Mongolian ethnic groups.
Amplification and expression of different myc‐family genes in a tumor specimen and 3 cell lines derived from one small‐cell lung cancer patient during longitudinal follow‐up
Authors: Kok Klaas , Osinga Jan , Schotanus Dick C. , Berendsen Henk H. , De Leu Lou F. M. H. , Buys Charles H. C. M.
Published: February 2007

In a small‐cell lung carcinoma (SCLC) tumor specimen as well as in 3 cell lines derived from SCLC biopsies obtained from the same patient at successive times during the clinical course, either the N‐myc gene or the c‐myc gene appeared to be amplified and expressed. The initial tumor specimen, a lymph‐node metastasis, was amplified for N‐myc, as was the cell line GLC‐14 derived from this metastasis. The cell lines GLC‐16 and GLC‐19, derived from recurrent primary tumor biopsies after a complete remission, were amplified for c‐myc. This finding implies independent amplification events and supports the idea that the amplification of myc genes is probably a secondary event correlated with tumor progression. Although all 3 cell lines could be classified as classic SCLC cell lines according to their histological characteristics, GLC‐16 and GLC‐19 clearly possess, in their c‐myc amplification and derivation from therapy‐resistant tumor cells, features of variant SCLC lines. This may question the significance of the classic/variant classification.
Detection of high concentrations of HTLV‐1 p24 and a novel gag precursor, p45, in serum immune complexes of a healthy seropositive individual
Authors: Schupbach Jorg , Kalyanaraman V. S.
Published: February 2007

Circulating immune complexes from sera of 6 patients with adult T‐cell leukemia and 8 asymptomatic carriers infected with the human T‐cell leukemia virus type I (HTLV‐I) were precipitated with polyethylene glycol, and the precipitates were tested for the presence of viral antigen p24 by Western blot, using affinity‐purified radiolabeled goat antibody to p24 as a probe. p24 and a larger protein of Mr 45,000 immunologically related to p24 were detected at concentrations of up to 100‐200 ng/ml in one of the carriers, while all other samples were negative. The concentration of the Mr 45,000 protein in the immune complexes was considerably higher than that of p24. Analysis of an HTLV‐I producer cell line, G‐II/MJ, by competition Western blots and gag‐speciiic antibodies, showed the presence of a hitherto unrecognized viral protein p45 which contains both p 19 and p24 and probably represents an intermediate precursor of these proteins. The results present direct evidence of production of HTLV‐1 proteins in an asymptomatically infected individual.
The transforming prototype of epstein‐barr virus (B95‐8) is also a lytic virus
Authors: Glaser Ronald , Tarr Kathleen L. , Dangel Andrew W.
Published: February 2007

The B95‐8 isolate of the Epstein‐Barr virus (EBV) has been described as a non‐lytic transforming virus. We have performed experiments in order to determine if the B95‐8 EBV is capable of super‐infecting and replicating in EBV‐genome‐positive non‐producer lymphoblastoid cells. Using concentrates of B95‐8 EBV, prepared from 6 different B95‐8 cell lines treated with l2‐O‐tetradecanoylphorbol‐13‐acetate (TPA), we demonstrated that virus concentrates could transform human or cotton‐top tamarin B‐lymphocytes and also lytically replicate in Raji cells, inducing EBV antigens and infectious virus. While the virus obtained from B95‐8 super‐infected Raji cells was able to transform cord‐blood lymphocytes (CBLs) and super‐infect Raji cells, transformation was abortive, with cell cultures only growing for up to 6 weeks. Transformation titers of the B9S‐8 virus concentrates ranged from 105 to > 108 transforming units/ml; early antigen (EA) induction ranged from 1% to 50% after superinfection of Raji cells, depending on the virus stock used, as determined by immunofluorescence. Southern blot analysis was carried out on the DNA prepared from B95‐8 cells and virion DNA. The results were consistent with the published EcoRI restriction pattern for B95‐8 EBV. The issue of whether the B95‐8 cells produce virions with a dual biological phenotype or, rather, 2 biologically distinct viruses, is addressed.
Expression of TGF‐α/EGF and TGF‐p receptors in human colon carcinoma cell lines
Authors: Murthy Uma , Anzano Mario A. , Greig Russell G.
Published: February 2007

Previous studies have established that colon carcinoma cells secrete several polypeptide growth factors, including TGF‐α/EGF and TGF‐ß, suggesting that these and related molecules function in an autocrine/paracrine fashion to modulate tumor‐cell growth. To investigate this possibility, we have studied the expression of transforming growth factor receptors in a panel of human colon carcinoma cell lines and in several untransformed epithelial cell populations. The results have revealed that neoplastic colon cells express receptors for both TGF‐α/EGF and TGF‐ß. Immunoprecipitation identified the TGF‐α/EGF receptor as a structurally intact 170‐kDa protein. No evidence for over‐expression was found. TGF‐α (and EGF) enhanced receptor autophosphorylation, indicating that these receptors were biochemically functional. TGF‐ß blocked DNA synthesis in non‐neoplastic epithelial cells but not in tumorigenic colon populations. There was no correlation with TGF‐ß receptor number or dissociation constant. However, chemical cross‐linking studies revealed a TGF‐ß receptor subtype of 75 kDa in 3 of the 4 colon carcinoma cells which was undetectable in normal IEC epithelial cultures, suggesting a possible association between 75‐kDa receptor expression and refractoriness to growth inhibition of TGF‐ß. Together, these data support the concept that locally‐produced growth regulators can function in an autocrine or paracrine manner to influence the proliferation of colon carcinoma cells.
Clonogenic cell assay for anchorage‐dependent squamous carcinoma cell lines using limiting dilution
Authors: Grenman Reidar , Burk David , Virolainen Erkki , Buick Ronald N. , Church John , Schwartz Donald R. , Carey Thomas E.
Published: February 2007

Clonogenic assays under either anchorage‐dependent or ‐independent conditions are very useful for testing the sensitivity of tumor cells to cytotoxic drugs and radiation. These assays have not been widely used with squamous‐cell carcinomas (SCC) because of poor tumor‐cell viability and poor cloning efficiency, especially in semi‐solid media. To find a clonogenic assay suitable for use with human squamous cancers we tested SCC lines, derived in our laboratory from patients with head and neck cancer, for the capacity to form colonies in soft agar and in 96‐well plates. Of 13 UM‐SCC lines tested for colony formation in agarose, only UM‐SCC‐11A was capable of growth in conventional semi‐solid media. One other line, UM‐SCC‐14C, produced colonies in agarose only in the presence of epidermal growth factor. In contrast, all 17 of the SCC lines tested exhibited colony formation in adherent cell culture using limiting dilution in 96‐well plates. The plating efficiencies of the SCC lines in the 96‐well plate assay ranged from 0.02 to 0.52 colonies (wells)/cell whereas the PE values in soft agar were lower, ranging from 0.0055 to 0.0086 colonies/ cell. The 96‐well plate assay is not affected by cell migration, a problem encountered with some cell lines when clonogenic assays are performed in Petri dishes. UM‐SCC‐11A was tested for radiation sensitivity both in soft agar and in the 96‐well plate assay. Comparable results were obtained. In summary, the majority of SCC cell lines did not form viable colonies in soft agar but the 96‐well plate assay was applicable to a broad spectrum of anchorage‐dependent human SCC cell lines and provides an efficient method for evaluating clonogenic cell survival.
Mechanism of mechanical trauma to ehrlich ascites tumor cells IN VITRO and its relationship to rapid intravascular death during metastasis
Authors: Weiss L. , Harlos J. P. , Elkin G.
Published: February 2007

Many, if not most, of the cancer cells arrested in the mi‐crovasculature during metastasis appear to be rapidly killed by mechanical trauma, associated with shape‐transitions, which require increases in cell surface area. The hypothesis has been advanced that such increases in surface area occur in 2 phases: First, there is an apparent increase due to surface unfolding, which is reversible and non‐lethal. Second, there is a true increase, during which cell surface membranes are stretched, with an increase in membrane tension. When tension exceeds a critical level, the surface membranes rupture and this irreversible change is lethal. In the present study, cell surface area has been incrementally increased by a hypotonic environment. Down to approximately 70 mM/kg, a reversible, non‐lethal increase in cell volume was observed, associated with electron microscopic evidence of unfolding. At and below 70 mM/kg, irreversible, lethal changes occurred, associated with increased susceptibility to the mechanical trauma associated with membrane‐filtration. These observations are consistent with the hypothesis in question.
Ganglioside GD3 shedding by human malignant melanoma cells
Authors: Bernhard Helga , Zum Büschenfelde Karl‐Hermann Meyer , Dippold Wolfgang G.
Published: February 2007

Gangliosides appear to be important target molecules for immunological effector mechanisms on neuro‐ectodermal tumors. Therefore in vitro studies were performed to examine whether ganglioside GD3, which is highly expressed on the cell surface of cultured human melanoma cells, is being shed into the culture medium. Measurable quantities of gangliosides GM3 and in particular GD3 were shed by the melanoma cells we have tested as detected on thin‐layer chromatograms (TLC) stained with orcinol. Ganglioside GD3 was also evidenced by immunoassaying with anti‐GD3 MAb and by ELISA. The concentration of GD3 in the supernatant of human melanoma cells depended on the ganglioside pattern of the cell line. Cells containing high levels of GD3 shed large amounts, cells with low levels shed no detectable GD3. Ganglioside GD3 was detectable in sera, but no major quantitative differences were observed in sera of patients with GD3‐positive tumors and normal controls. This points to a local accumulation of ganglioside GD3 at the tumor site.
Benzoyl peroxide enhances the invasive ability of a mouse epidermal carcinoma cell line
Authors: Bonfil R. D. , Momiki S. , Conti C. J. , Klein‐Szanto A. J. P.
Published: February 2007

The effect of the skin tumor promoter benzoyl peroxide on the invasive potential of a murine squamous carcinoma cell line was investigated using an in vitro assay based on the capacity of cells to migrate through a porous filter coated with matrigel. Pre‐treatment of the murine squamous carcinoma cell line CH72 with benzoyl peroxide added to the tissue culture medium increased the invasive capacity of these cells 5‐8 times. No effects were observed on cells from primary cultures of normal murine epidermis. The simultaneous treatment of CH72 cells with benzoyl peroxide and the free radical scavengers, superoxide dismutase or CuS04, prevented the increase and the values did not differ significantly from the baseline invasive potential. This suggests that activated oxygen species participate in the benzoyl peroxide‐induced enhancement of the invasive capacity of these carcinoma cells.
Oncogene expression in small‐cell lung cancer cell lines and a testicular germ‐cell tumor: Activation of the N‐myc gene and decreased RB mRNA
Authors: Saksela Kalle , Mäkelä Tomi P. , Alitalo Kari
Published: February 2007

N‐myc and L‐myc proto‐oncogenes are expressed in many developing embryonic tissues. In contrast to expression of the closely related c‐myc gene, N‐myc and L‐myc expression is very restricted in adult tissues. We show that small amounts of the L‐myc RNA can be detected in normal adult testicular tissue. A high level of N‐myc expression from a single‐copy N‐myc gene was found in a malignant tumor of the testis, histopathologically defined as a seminoma. This tumor also showed a decrease of mRNA from the retinoblastoma gene (RB), which is ubiquitously expressed in all normal tissues. Strikingly similar results on elevated expression of the L‐myc and N‐myc genes and a lack of RB mRNA have been reported in small‐cell lung cancer cell lines, and are confirmed in our study.
Quantification of epidermal growth factor in human breast cyst fluids: Correlation with dehydroepiandrosterone‐sulphate and electrolyte concentrations
Authors: Smith K. , Miller W. R. , Fennelly J. A. , Matthews J. N. S. , Scott W. N. , Harris A. L.
Published: February 2007

Epidermal growth factor (EGF), dehydroepiandrosterone (DHA)‐sulphate and [Na+] and [K+] were assayed in 78 cyst fluids from patients with a palpable breast cyst. Epidermal growth factor was detected in all but 2 cysts, the mean value ± Sem being 506.2 ± 39.3 ng/ml, with a range of 0‐1,599 ng/ml. When the cyst fluids were sub‐divided according to their [Na+]:[K+] ratio, group A cyst fluids ([Na+]:[K+] < 3) had a significantly higher (p < 0.001) level of EGF than group B cyst fluids ([Na+]:[K+] > 3). Furthermore, the relationship between EGF and [Na+] and [K+] and between EGF and DHA‐sulphate seemed to differ between the 2 cyst types and each cyst type was therefore analyzed separately.
Sucrase‐isomaltase expression and enterocytic ultrastructure of human colorectal tumors
Authors: Czernichow Bella , Simon‐Assmann Patricia , Kedinger Michele , Arnold Christiane , Parache Michel , Marescaux Jacques , Zweibaum Alain , Haffen Katy
Published: February 2007

We report the relative frequency of sucrase‐isomaltase (SI) antigen expression in human colonic adenocarcinoma (22/57), in peritumoral mucosa taken next to the tumor (31/41) or distant from it (29/42) as well as in 21/23 polyps. Our results are based on indirect immunofluorescence with a monoclonal antibody (MAb) specific for human intestinal SI. A regular and intense expression of SI occurred only in 6 tumor specimens. In the remaining 16 Sl‐positive tumor samples, labelling was heterogeneous, i.e., scattered over more or less extensive areas. A similar irregular staining pattern was also found in polyps and in peritumoral mucosa, irrespective of its distance from the tumor. Electron microscopic examination of 19 carcinomas mostly revealed altered brush‐border membrane features, irrespective of histological SI staining pattern. Brush‐border enzyme activities of sucrase, alkaline phosphatase and maltase showed no difference between tumor specimens and peritumoral mucosa, but aminopeptidase was depressed in the former. Sucrase activity was extremely low (mean values 1.1 to 1.8 mU/mg protein) and rose only exceptionally to 17.5 mU/mg prot.
t(2;8) variant translocation in burkitt's lymphoma: Mapping of chromosomal breakpoints by in situ hybridization
Authors: Adolph Sabine , Hameister Horst , Henglein Berthold , Lipp Martin , Hartl Peter , Baas Frank , Lenoir Gilbert , Bornkamm Georg W.
Published: February 2007

In 6 different Burkitt lymphoma cell lines with t(2;8) variant translocations (JI. LY66, LY9I, BL21, BL64, JBL2) the breakpoints on chromosome 8q+ were mapped in relation to each other and to c‐myc by in situ hybridization. The probes used were derived from chromosome 8q24 and comprised a c‐myc probe, a probe located 48 kb downstream of c‐myc, 3 probes adjacent to the chromosomal breakpoints of BL64, LY91 and JBL2, respectively, and 2 probes located in the 5′ and 3′ part of the thyroglobulin gene. The breakpoints of LY91 and JBL2 lie <200 kb and>200 kb downstream of c‐myc, whereas the distance to c‐myc of the BL64 breakpoint and of the thyroglobulin probes is unknown. By recording the hybridization signals specific for these probes on chromosomes 2p− and 8q+of each cell line it was possible to establish the order of breakpoints on band 8q24 relative to the c‐myc and thyroglobulin genes as follows: centromere—c‐myc—JI—BL64—BL21— LY91—JBL2—LY66—thyroglobulin—telomere. This information is essential for further mapping of this important chromosomal region.
Characterization of cell lines derived from a multiply aneuploid human bladder transitional‐cell carcinoma, UCRU‐BL‐13
Authors: Russell Pamela J. , Wass Jane , Lukeis Robyn , Garson O. Margaret , Jelbart Margaret , Wills Edward , Philips Jeanette , Brown Joanne , Carrington Nigel , Vincent Paul C. , Raghavan Derek
Published: February 2007

A series of cultured cell lines (designated UCRU‐BL‐13) has been established from different serial passages of a multiply aneuploid human bladder transitional‐cell carcinoma xenografted in nude mice. Serial passage of the xenografts in vivo and of the cell lines in vitro was accompanied by shifts in the tumor ploidy, with dominance of different major peaks. Despite this, the expression of tumor markers remained constant, and consistent chromosomal markers were observed both in the 8th xenograft passage and in a subline in tissue culture established over a year apart. Chromosomal numbers reflected the predominant aneuploid peaks observed; consistent numerical and structural changes included a marker derived from chromosome I, 8p−, −10, 11q +, and I7q+. The cell line derived from the initial xenograft comprised a mixture of transitional, adenocarcinoma and squamous carcinoma cells in early passage, but adenocarcinoma cells were absent from later passages. The lines expressed the B‐blood‐group antigen, histocompatibility antigens, receptors for transferrin and EGF, and reacted with a series of monoclonal antibodies (MAbs) directed to malignant human epithelial cell lines. These lines provide a model for studying the evolution of tumor heterogeneity and drug resistance in bladder carcinoma exhibiting multiple aneupioidy.
Diverse responses to retinoid in morphological differentiation, tumorigenesis and n‐myc expression in human neuroblastoma sublines
Authors: Hino Tamaki , Sugimoto Tohru , Matsumura Takafumi , Horii Yoshihiro , Inazawa Johji , Sawada Tadashi
Published: February 2007

We established the subline RT‐BMV‐C6 from the parent human neuroblastoma cell line RT‐BM by a process that required repeated subculture of cells, which were prone to disaggregation. RT‐BMV‐C6 and the parent cloned line, RT‐BM‐I, had an identical marker chromosome, confirming that both lines were derived from a common progenitor. In the analysis of surface antigen expression, RT‐BMV‐C6 did not react with UJ‐127‐11, Leu7 or KP‐NAC2 MAbs to which RT‐BM‐I showed positive binding. The levels of both N‐myc amplification and expression in RT‐BMV‐C6 were twice as high as the level obtained in RT‐BM‐I. Colony‐forming efficiency in soft agar was 2.0 ± 0.8% for RT‐BMV‐C6 and 3 times greater than that for RT‐BM‐I (0.6 ± 0.1%). When 100 × 106 cells of RT‐BM‐I and RT‐BMV‐C6 were inoculated into nude mice, tumor incidence was significantly higher for RT‐BMV‐C6 (6/6; 100%) than for RT‐BM‐I (0/6; 0%). Our data show that N‐myc is closely related to tumorigenicity in NB. When RT‐BM‐I and RT‐BMV‐C6 were co‐cultured with a new synthetic retinoid, polyprenoic acid (E5166), and dibutyryi cyclic AMP, RT‐BM‐I was induced to neuronal differentiation, defined by the formation of neuronal processes and expression of neurofilaments, whereas RT‐BMV‐C6 was not. However, when exposed to E5166, N‐myc expression of RT‐BMV‐C6 was more strongly reduced than that of RT‐BM‐I, and colony formation of RT‐BMV‐C6 was significantly inhibited as compared to RT‐BM‐I. These findings suggest that the reduction of N‐myc expression might closely correlate with growth inhibition accompanying neuronal differentiation of neuroblastoma cells.
Comparison of therapeutic efficacy and host toxicity of two different 131I‐labelled antibodies and their fragments in the GW‐39 colonic cancer xenograft model
Authors: Blumenthal Rosalyn D. , Sharkey Robert M. , Kashi Rina , Goldenberg David M.
Published: February 2007

The in vivo uptake, therapeutic potential, and host toxicity were evaluated for both the intact IgG and F(ab′)2 fragment of 2 murine monoclonal antibodies (MAbs) directed against either carcino‐embryonic antigen (CEA), called NP‐4, or colon‐specific antigen‐p (CSAp), called Mu‐9, in the GW‐39 human colorectal carcinoma grown in the hamster cheek pouch. Mu‐9 IgG and F(ab′)2 were retained longer by the tumor than was the NP‐4 IgG or F(ab′)2, respectively. Localization of the two antibodies by micro‐autoradiography revealed two distinct patterns. Mu‐9 was seen densely around whole acini of tumor cells, whereas NP‐4 was found around each individual cell, albeit less densely. The anti‐tumor effects of 131l‐labelled Mu‐9 and NP‐4 IgG were equal, but the therapeutic effectiveness of Mu‐9 F(ab′)2 was significantly higher than NP‐4 F(ab′)2, as measured by change in tumor size. A dose‐dependent increase in host toxicity, as measured by change in body weight and change in peripheral white blood cells (p‐WBCs), was observed with 0.S to 3.0 mCi doses of 131l‐lgG regardless of the MAb used. A 10‐22% loss in body weight lasting 3‐7 weeks and a 50‐80% loss in pWBCs lasting 6‐8 weeks were observed in these animals. In contrast, 3 × 2 mCi doses of 131l‐NP‐4 or Mu‐9 F(ab′)2 given at 3‐day intervals, a schedule which was equally therapeutic to a single 2‐mCi dose of 131l‐lgG, resulted in only a 9% loss in body weight and a 50% loss in pWBCs that lasted only I week. This was followed by a complete recovery over the next 2‐3 weeks. These data suggest that multiple doses of F(ab′)2 can be as tumoricidal as a single dose of an intact MAb IgG, but significantly less toxic to the host.
Zn++ inhibits both tumor necrosis factor‐mediated DNA fragmentation and cytolysis
Authors: Flieger Dimitri , Riethmüller Gert , Ziegler‐Heitbrock H. W. L.
Published: February 2007

The cellular events involved in direct tumor‐cell destruction by tumor necrosis factor (TNF) are still incompletely understood, but a role of endonucleases has been suggested. In the present study we have analyzed in detail the effect of Zn++, an inhibitor of endonucleases, on TNF‐mediated DNA‐fragmentation and on cytolysis in Actinomycin‐D‐pre‐treated WEH1164‐S cells. Beginning 2 hr after addition of TNF, a rapid degradation of cellular DNA is observed, as evidenced by release of 3H‐Thymidine (TdR) label from nuclei into cytoplasm. TNF‐mediated lysis of WEH1164‐S cells begins at 3 hr and reaches plateau levels at 7 hr. Addition of Zn++ to TNF‐treated WEH1164 cells completely abrogates DNA fragmentation at 1mM. Of greater importance is the fact that Zn++treatment also completely blocks TNF‐mediated cytolysis of the target cells. Concentrations between 0.1 and I mM ZnSO4prevent cell death, as assessed by chromium‐release and Trypan blue dye exclusion. In addition, ZnCI2, but not other divalent cations like CaCI2, MgSO4 and CuSO4 in the same concentration range, prevents cell death as well, demonstrating that the effect in fact is mediated by Zn++. Zn++ added 2 hr after TNF treatment, still effectively inhibits cell lysis, indicating that it acts at a late stage after binding of TNF to its receptor. Our data suggest that activation of endonucleases is not an accompanying effect but an essential step in TNF‐mediated tumor‐cell destruction.
Sterically hindered analogues of diacylglycerols. synthesis, binding to the phorbol ester receptor and metabolism in a549 human lung carcinoma cells
Authors: Laughton Charles A. , Bradshaw Tracey D. , Gescher Andreas
Published: February 2007

The 5 following compounds were synthesized in order to investigate the relationship between structure and ability of glyceride‐type molecules to bind to the phorbol ester receptor: one dioctanoyl cyclohexane‐1,2,4‐triol, 2 isomeric methyl analogues of 1,2‐dioctanoyl‐sn‐glycerol (diC8), one dimethyl and one cyclohexyl analogue of diC8. Their ability to compete with 3H‐labelled phorbol‐12,13‐dibutyrate ([3H]PDBu) for specific binding sites in intact A549 human‐derived lung carcinoma cells and in a cytosolic cell extract was compared with that of diC8 and l2‐O‐tetradecanoylphorbol‐13‐acetate (TPA). The affinity of diC8 for the phorbol ester receptor was much weaker than that of TPA. The analogues in turn were less able than diC8 to compete with [3H]PDBu for receptor sites. Like diC8 and unlike TPA, the synthesized compounds inhibited cell growth only at those concentrations at which cytotoxicity was also apparent. DiC8 and its methyl and dimethyl derivates, but not the cyclohexyl derivative or the cyclohexanetriol diester, were metabolically removed from cellular incubates as measured by gas liquid chromatography. The results suggest that the binding of glyceride‐type molecules to the phorbol ester receptor exhibits stringent specificity and that the design of novel potent agonists of phorbol esters might require the placement of the molecular features of diacyiglycerols important for biological activity into a molecular framework which is more complicated than glycerol.
Effect of immunization on HTLV‐I infection in rabbits
Authors: Takehara N. , Iwahara Y. , Uemura Y. , Sawada T. , Ohtsuki Y. , Iwai H. , Hoshino H. , Miyoshi I.
Published: February 2007

Two groups of 3 rabbits, each immunized with heat‐inactivated HTLV‐I or a synthetic env peptide (env175‐l96), developed antibodies to viral proteins including gp68 and gp46. These immunized rabbits were then challenged with a transfusion of blood from HTLV‐I‐infected rabbits of the opposite sex. After transfusion challenge, antibody titers further rose in both groups and antibodies to HTLV‐I proteins p24 and p 19 newly appeared in the env 175‐196 group. In addition, 3 more rabbits were infused with hyperimmune rabbit anti‐HTLV‐I IgG and similarly challenged with virus‐infected blood. Pre‐challenge sera from these rabbits showed high anti‐HTLV‐I titers with antibodies to envelope and core proteins. Despite transfusion challenge, the antibody titers gradually declined to undetectable levels in all 3 rabbits over a period of 16 weeks. Virus isolation was attempted from peripheral lymphocytes harvested 1 to 6 months after challenge infection and cultured in the presence of interleukin‐2 (IL‐2). HTLV‐I‐carrying lymphoid cell lines of recipient origin were established from all 6 rabbits given active immunization, whereas HTLV‐I could not be isolated from any of the 3 rabbits given passive immunization. Absence of virus infection in the latter group was confirmed by negative blood transfusion assay to normal rabbits. These results indicate that hyperimmune IgG, but neither heat‐inactivated HTLV‐I nor env 175‐196, were protective against HTLV‐I infection induced by blood transfusion.
Plasmacytoma induction in radiochimeras
Authors: Silva Santiago , Babonits Magda , Wiener Francis , Klein George
Published: February 2007

We have induced plasmacytomas (MPC) in BALB/c radio‐chimeras (RCh) repopulated with syngeneic hemopoietic cells carrying distinctive chromosomal markers. A group of 38 RCh that received 0.5 ml pristane, followed by Abelson virus infection 2‐3 weeks later, developed 7 tumors (18.5%) of donor origin after a relatively short latency period (X = 83 ± 8.3 days). In contrast, only 3 (2%) MPCs were observed in 149 RChs that received 0.5 ml pristane 3 times at monthly intervals. Two of them originated from host cells. Pristane‐treated RChs developed a less extensive oil granuloma (OG), compared with pristane‐treated intact mice. This may explain the low incidence of MPC in the former. Our findings also suggest that Abelson virus can overcome the postulated deficiency of OG. MPC induction in the pristane + Abelson‐virus‐treated RCh system will facilitate the further characterization of the MPC precursor cell and the localization of genetic resistance vs. susceptibility factors at the donor vs. host level.
Reduced cell adhesion to fibronectin and laminin is associated with altered glycosylation of β1, integrins in a weakly metastatic glycosylation mutant
Authors: Öz Orhan K. , Campbell Allyson , Tao Tien‐Wen
Published: February 2007

A weakly metastatic wheat‐germ‐agglutinin‐resistant mutant Wa4‐b I was previously shown to be less adherent to endothelial cell extracellular matrix than the more metastatic parental B‐16 melanoma cells. This report describes reduced adhesion and spreading of Wa4‐bI cells on the cell‐binding domain of fibronectin (CBD) and laminin (LN). Cell surface receptors which mediate such interactions are members of the integrin family of membrane glycoproteins. An antibody that recognizes the 3, integrin subunit inhibited spreading on both the CBD and LN. The integrins of the mutant cells immunoprecipitated by the antibody appeared to be structurally altered, showing a greater electrophoretic mobility. The mobility difference between the parent and the mutant receptors was abolished following removal of the glycan moieties of the receptors enzymatically using glycopeptidase F, or chemically using trifluoromethanesulfonic acid, suggesting that the structural alteration of the mutant receptors is in glycosylation. The altered receptors may be responsible for the observed decrease in cell adhesion and spreading of the mutant cells to the CBD and LN. Such a decrease in Wa4‐bI cell interaction with extracellular matrix components may play a role in their decreased metastatic potential.
Relative tumorigenicities of hybrid cells with and without hsr‐bearing chromosomes from a human melanoma cell line
Authors: Hough Margaret R. , White Bradley N. , Holden Jeanette J. A.
Published: February 2007

Some cell types within the human melanoma cell line MeWo contain homogeneously staining regions (HSRs) consisting of repetitive DNA sequences and ribosomal RNA (rRNA) genes derived from chromosome 15. To further examine the association between enhanced tumorigenicity and the presence of HSR‐bearing chromosomes, hybrid cell lines were constructed by fusing X‐HSR‐containing MeWo cells with ouabain‐resistant, HPRT‐deficient Chinese hamster ovary cells and culturing in HAT medium containing ouabain. A hybrid containing the X‐HSR chromosome and several MeWo chromosomes was more tumorigenic in BALB/c nude mice than derivative cells lacking the X‐HSR and human chromosome 18. However, since this enhanced tumorigenicity could be due to sequences on either the X‐HSR or chromosome 18, a second series of hybrids was constructed by micro‐cell fusion. In this case, the tumorigenicity of hybrid cells containing 2 copies of the X‐HSR as the only MeWo chromosome was similar to that of derivative cells lacking these chromosomes. Cytogenetic analysis revealed that the nucleolar organizer regions (NORs) on the HSR were inactive in the hybrid cells. Our data indicate that DNA sequences amplified on MeWo HSRs do not enhance tumorigenicity under experimental conditions in which rRNA genes are not expressed. As the only active NORs in MeWo HSR‐containing cells are on the HSRs, we suggest that expression of these amplified rRNA genes is responsible for the selective growth advantage of these cell types in nude mice. Our data also indicate that the enhanced tumorigenicity of MeWo HSR‐containing cells is not due to co‐amplification of a dominant oncogene.
Molecular cloning and characterization of endogenous SV40 dna from human HBL‐100 cells
Authors: Saint‐Ruf C. , Nardeux P. , Cebiuan J. , Lacasa M. , Lavialle C. , Cassingena R.
Published: February 2007

The human HBL‐100 cell line harbours SV40 DNA integrated in tandem at a unique site. The SV40 T‐antigen expressed in these cells is defective in a function essential to the replication of the viral genome. The integrated SV40 sequences were molecularly cloned in a bacteriophage, and a subclone (plasmid pSVHBI) containing a complete SV40 DNA was isolated. As compared to SV40 wild‐type strain 776, sequence analysis of pSVHBI early region revealed the presence of several DNA alterations. Among these, a point mutation at position 3199, predicting a change at amino‐acid 540 of arginine to isoleucine, was shown by marker rescue to be responsible for the deficiency of T‐antigen. This novel mutation further delimits one of the T‐antigen domains involved in SV40 DNA replication. Transfection experiments demonstrated that the transforming activity of the SV40 genome from HBL‐100 cells is still preserved. Moreover, several transformed human cell clones thus obtained could be permanently established in culture.
Seroepidemiologic survey for antibodies to human retroviruses in human and non‐human primates in Brazil
Authors: Andrada‐Serpa Maria José , Tosswill Jennifer , Schor Doris , Linhares Denise , Dobbin Jane , Pereira Marguerite S.
Published: February 2007

The prevalence of antibodies to HTLV‐I and HIV‐I in Brazil was determined by testing sera from: (a) 119 members of an isolated Amazonian community of African origin; (b) 100 voluntary blood donors in Rio de Janeiro; (c) 215 patients treated at the Hematology Service, National Cancer Institute, Rio de Janeiro, and (d) 44 Cebus apella New World monkeys, wild‐caught in Amazonia. Anti‐HTLV‐I was detected in I (0.84%) of 119 Amazonians, in 8 (3.72%) of the 215 patients and in none of the blood donors or monkeys. The high prevalence found in patients included 4 (5.79%) of 69 with non‐Hodgkin lymphoma, 2 (5.88%) of 34 with Hodgkin lymphoma, I (16.66%) of 6 patients with diagnosis of anemia and I (20%) of 5 with HIV‐I infection. Anti‐HIV‐l was found in 7 (14.89%) of 47 patients and in none of the other groups. The high incidence of HTLV‐I infection in the patient group suggests that this retrovirus is endemic in parts of Brazil.
Expression of TGF‐β and procollagen type I and type III in human gastric carcinomas
Authors: Yoshida Kazuhiro , Yokozaki Hiroshi , Niimoto Minoru , Ito Hisao , Ito Masanori , Tahara Eiichi
Published: February 2007

To elucidate the difference between scirrhous and non‐scirrhous gastric carcinomas, we examined the expressions of TGF‐β, procollagen type I and type III in 7 gastric carcinoma cell lines and 37 gastric carcinoma tissues, and also examined the effect of TGF‐β on the expression of procollagen mRNA by TMK‐I cells. TGF‐β mRNA was detected in all the tumors examined in vivo and in vitro. Interestingly, 9 (90%) of 10 scirrhous gastric carcinomas revealed higher levels of TGF‐β mRNA than normal tissues, while 8 (38%) of 21 well‐differentiated adenocarcinomas had higher TGF‐β mRNA levels than normal tissues. As for procollagen mRNA, most of the human gastric carcinoma cell lines expressed type‐l procollagen mRNA and MKN‐I expressed type‐Ill procollagen mRNA. Furthermore, procollagen type‐l mRNA accumulation in TMK‐I cells was increased by exogenous TGF‐β. Most of the tumor tissues from surgical specimens expressed higher procollagen mRNA than normal tissues. These results indicate that TGF‐β produced by carcinoma cells might stimulate collagen synthesis not only by fibroblasts but also by carcinoma cells themselves, leading to diffuse fibrosis of scirrhous gastric carcinomas.
Histologic types of breast carcinoma in relation to international variation and breast cancer risk factors
Authors: Stalsberg H. , Thomas D. B. , Noonan E. A. ,   The Who Collaborative Study of Neoplasia and Steroid Contraceptives, Berry G. , Maclennan R. , Shearman R. , Jelihovsky T. , Booth J. Cooper , Molina R. , Martinez L. , Salas O. , Dabancens A. , Zhiheng Chen , Yun Tao , Wei Hu Yong , Cuadros A. , Aristizabal N. , Ebeling K. , Nishan P. , Kunde D. , Modan B. , Ron E. , Alfandary E. , Mati J. G. , Kenya P. , Kungu A. , Gatei D. , Cuevas H. Rodriguez , Salazar S. Benavides , Palet A. , Ontiveros P. , Apelo R. A. , De Cruz J. R. La , Baens J. , Javier B. , Silpisornkosol Suporn , Pardthaisong Tieng , Martin Nimit , Theetranont Choti , Boosiri Banpot , Chutivongse Supawat , Virutamasen Pramuan , Wongsrichanalai Chansuda , Jimakorn Prasarn , Koetsawang Suporn , Rachawat Daungdao , Chantarakul Nivat , Holck S.
Published: February 2007

Associations between breast cancer risk factors and histologic types of invasive breast carcinoma were studied in 2,728 patients. Lobular and tubular carcinomas occurred with increased relative frequency in most high‐risk groups. The proportion of these types increased with age to a maximum at 45–49 years and decreased in the following decade. Significantly increased proportions of lobular and tubular carcinomas were also associated with high‐risk countries, prior benign breast biopsy, bilateral breast cancer, concurrent mammary dysplasia, high age at first live birth, never‐pregnant patients compared to those with a first live birth before age 20, private pay status, and length of education. Nonsignificant increases were associated with family history of breast cancer, less than 5 live births, less than 25 months total of breast feeding, use of oral contraceptives or IUD, and high occupational class. As a general trend, the higher the overall relative risk, the higher the proportion of lobular and tubular carcinomas. The occurrence of other histologic types also increased with increased breast cancer risk, but to a smaller degree than for lobular/tubular carcinomas. It is suggested that all hormonally related, socio‐economic and geographic risk factors exert their effect by selectively increasing the number of lobular cells at risk. Family history of breast cancer and age over 49 years did not follow the general trend of parallel increases in the proportion of lobular/tubular carcinomas and breast cancer risk, and may operate through other mechanisms.
Colorectal carcinoma in Hong Kong Chinese. A pathological survey of 1,117 cases, 1972–1981
Authors: Collins Robert John , Chan Chi‐Wing
Published: February 2007

Hong Kong Chinese, when compared with the world population, have an intermediate incidence rate for colorectal carcinoma. The purpose of this retrospective analysis of a large number of colorectal carcinomas (1,117 cases) was to explore possible differences between this series and others, and to re‐examine the divergent features reported in a smaller series. The present study revealed a distribution by age, sex, site and Dukes' stage, as well as histopathological features, which were analogous to those reported from other countries. Thus, while the incidence is lower in this group, the other manifestations of the disease are very similar to those seen elsewhere. The implication is that, apart from varying incidence, there is a global similarity among colorectal tumours.
Familial susceptibility to breast cancer: A complex inheritance
Authors: Andrieu Nadine , Clavel Françoise , Demenais Florence
Published: February 2007

The main results of segregation analysis aimed at identifying a major genetic factor involved in susceptibility to breast cancer are reviewed. They show that the existence of a single major gene is not sufficient to explain the distributions of the disease observed in the families concerned and suggest that the genetic inheritance involved is heterogeneous and complex. Heterogeneity has been explored in various studies according to epidemiological criteria. From these analyses, genetically homogeneous subgroups emerged (for instance families with breast cancer only or with affected males). The study of such homogeneous subgroups might help to better locate the susceptibility gene(s) on the chromosome map by analysis of genetic linkage using different markers. The results of segregation analysis depend on how epidemiological factors are taken into account. It is of major importance that epidemiological data on the proband (i.e., the individual prompting selection of a family) as well as on the members of his/her family are taken into consideration to improve understanding of the complexity of breast cancer transmission.
Generation of a recombinant mouse‐human chimaeric monoclonal antibody directed against human carcinoembryonic antigen
Authors: Hardman Norman , Gill L. Lee , de Winter Ronald F. J. , Wagner Kathrin , Hollis Melvyn , Businger Felix , Ammaturo Domenico , Buchegger Franz , Mach Jean‐Pierre , Heusser Christoph
Published: February 2007

A procedure was devised for the identification and specific cloning of functionally rearranged variable region immunoglobulin (Ig) gene segments from genomic DNA of a murine hybridoma cell line which produces a high‐affinity monoclonal antibody (MAb) directed against human carcinoembryonic antigen (CEA). The cloned, functionally‐rearranged murine Ig H‐chain and L‐chain variable region gene segments were incorporated into plasmid vectors capable of directing the expression of a chimaeric mouse‐human antibody molecule with human (Y4,K) constant region sequences. Expression plasmids were transfected into a mouse myeloma cell line by electro‐poration and transfectomas secreting functional chimaeric antibody selected. Chimaeric antibody generated by transfectomas was analysed and shown to compete effectively with its murine counterpart for binding to the CEA epitope, and to have an equivalent antigen‐binding affinity. This anti‐CEA recombinant antibody should find application in in vivodiagnosis by immunoscintigraphy of human colonic carcinoma, and possibly also in therapy of the disease, overcoming some of the difficulties associated with the repeated use of non‐human immunoglobulins in human patients.