bluuebunny/crossref_metadata_2025 huggingface dataset:
Leukemia serum reactive with retrovirus‐related antigen in normal human placenta
Authors: Maeda Shuichi , Yonezawa Kazuhiko , Yoshizaki Haruyasu , Mori Masamitu , Kobayashi Takeaki , Akahonai Yoshikazu , Yachi Akira , Mellors Robert C.
Published: February 2007

Serum antibody reactive with a retrovirus‐related p30 antigen in human normal term placenta was investigated and characterized by immunohistologic and immunoblotting methods. Sera obtained from patients with acute leukemia and malignant lymphoma were used as first antibody, and cryostat sections of placenta were the target antigen. An IgM antibody that reacted mainly with the basal aspect of syncytio‐ trophoblast of chorionic villi, where a putative human endogenous retrovirus p30 antigen is located, was directed by indirect immunofluorescence. This antibody activity, termed anti‐basal aspect of syncytiotropho‐ blast (anti‐BAST), was detected in the sera of many patients with acute leukemia (AML, ALL) and malignant lymphoma, and less frequently in sera of pregnant women and normal controls. As shown by immunoblotting analysis, the main reactive antigen recognized by anti‐BAST was a non‐glycosylated 32‐ kDa placental protein which was antigenically related to SSAV p30. A non‐glycosylated 19‐kDa protein was also considered to be one of the anti‐BAST‐corresponding antigens. This suggests the presence of a new antigen‐antibody system of human retrovirus(es) revealed by subinfectious antigenic expression and by specific antibody activity in conditions of human health and disease, particularly, acute leukemias and malignant lymphomas of common types.
CO‐reversion of a lectin‐resistant mutation and non‐metastatic phenotype in murine tumor cells
Authors: Dennis J. W. , Laferte S.
Published: February 2007

Three independent isolates, one obtained spontaneously and the others obtained after in vitro mutagenesis, of a WGA‐resistant mutation were compared to the highly metastatic parental murine cell line MDAY‐D2 for alterations in plasma membrane glycoproteins and changes in metastatic behavior. The mutants were non‐metastatic from an s.c. site of injection and poor organ‐colonizers when administered i.v. Each of the mutant lines had the same lesion in N‐linked oligosaccharide structure, which rendered the cells hypersensitive to the N‐acetylglucosamine‐binding lectin BSII in vitro. The phenotypic similarities between the 3 WGA‐resistant isolates indicated that the mutation was directly related to the attenuated malignant phenotype. Direct confirmation was obtained by the isolation of a BSII‐resistant clone of the mutant cells that co‐reverted for lectin‐sensitivity, lectin binding glycoproteins and malignant aggressiveness. The results indicate a direct relationship between malignant behavior and cell‐surface oligosaccharide structure.
A monoclonal antibody reacting with endothelial cells of budding vessels in tumors and inflammatory tissues, and non‐reactive with normal adult tissues
Authors: Hagemeier Hans‐Hermann , Vollmer Ekkehard , Goerdt Sergij , Schulze‐Osthoff Klaus , Sorg Clemens
Published: February 2007

This report describes a monoclonal antibody (MAb) generated by immunization of mice with cell suspensions of capillary‐rich fragments of mammary carcinomas. The antibody (EN 7/44) belongs to the IgM class and detects a 30.5 kDa antigen which is found in the cytoplasm of human placental and umbilical veinendothelial cells (HUVEC) and on the surface of tumor endothelium. Using indirect immunofluorescence and immunoperoxidase techniques, we did not find the MAb in peripheral blood cells or in any human cell lines tested, nor in endothelial cells from normal, non‐proliferating adult tissues. Positively staining endothelium was found in the placenta, the umbilical vein and in proliferating normal tissues (intestine). Positive endothelial cells were found in acute inflammatory reactions and in tumors. In the latter, the strongest reactions were seen in newly formed budding capillaries, which were identified by their reactivity with Ulex europaeus I‐lectin and antibodies against F VIM‐RAG. In tumor tissues, large vessels could be positively stained with the EN 7/44 antigen, in contrast to inflammatory tissues. It is concluded that endothelial cells at the tip of a budding capillary express distinct phenotypic characteristics.
A case‐control study of the efficacy of a non‐randomized breast cancer screening program in florence (Italy)
Authors: Palli Domenico , del Turco Marco Rosselli , Buiatti Eva , Carli Simona , Ciatto Stefano , Toscani Lucia , Maltoni Giancarlo
Published: February 2007

In a rural area near Florence a population‐based screening program for breast cancer was started in 1970, offering a mammography test every 2.5 years to all women between 40 and 70 years of age. In order to evaluate the efficacy of this program a case‐control study has been carried out comparing the screening history of all women who died from breast cancer in this area in the years 1977–1984, and who had been diagnosed after the start of the program, with that of a matched group of living controls. The case‐control study showed that the overall O.R. of dying from breast cancer in the study period for “screened” versus “never‐screened” women was 0.53 (95% C.I. = 0.29–0.95). After evaluation of other variables as potential confounders the adjusted O.R. estimates were respectively 0.57 (95% C.I. = 0.35–0.92) and 0.32 (95% C.I. = 0.20–0.52) for women screened only once or at least twice. No significant protective effect was shown for women below the age of 50 years.
Phenotypic profile of clones from early cultures of human metastatic melanomas and its modulation by recombinant interferon γ
Authors: Anichini Andrea , Mortarini Roberta , Fossati Giuseppe , Parmiani Giorgio
Published: February 2007

Fifty‐six tumor clones isolated by cloning in soft agar from early cultures (before the 10th in vitro passage) of two different human metastatic melanomas (Me9229 and Me28) were characterized by FACS analysis for surface expression of class‐I and class‐II HLA antigens and of melanoma‐associated antigens (MAA) with a panel of 15 monoclonal antibodies (MAbs). A marked phenotypic heterogeneity involving MAA and/or HLA markers was observed among the clones derived from both tumors. The differences among the tumor clones and between them and the uncloned melanoma were qualitative and quantitative for each antigen considered. Clones derived from Me9229 expressed the same HLA profile as the parental culture (class I +, class II‐) while strong heterogeneity was observed for MAA expression. Clones from Me28 presented a marked heterogeneity for class‐I and class‐II HLA antigens but were more homogeneous for MAA. The phenotype of the clones was repeatedly checked over the first month in culture and found to remain generally unchanged and not linked to the cell cycle. However, major changes in antigenic expression of the clones could be observed upon treatment with recombinant interferon‐γ (rIFN‐γ): class‐I and‐II HLA antigens could be induced or augmented while a moderate inhibition was seen on MAA expression. Furthermore, an apparent hierarchy in expression and/or induction of class‐II antigens by rIFN‐γ was observed among the tumor clones. DR antigens were more frequently expressed (Me28 clones) and upon treatment with HFN‐γ reached higher levels than DP and DQ products. Taken together these results indicate that antigenic heterogeneity for MAA and HLA antigens can be detected in cells isolated from early cultures of human metastatic melanomas and suggest that the original uncloned tumor might be considered as a complex mixed population made up of a number of neoplastic cells each expressing a distinct phenotype which can be modulated by lymphokines such as IFN‐γ.
Two new cell lines from B‐prolymphocytic leukaemia: Characterization by morphology, immunological markers, karyotype and Ig gene rearrangement
Authors: Melo Junia V. , Brito‐Babapulle Vasantha , Foroni Letizia , Robinson Daniele S. F. , Luzzatto Lucio , Catovsky Daniel
Published: February 2007

Leukaemic cells from 2 patients with B‐prolymphocytic leukaemia were immortalized in vitro by means of Epstein‐Barr virus and phorbol‐ester TPA. The resulting cell lines, named JVM‐2 and JVM‐3, have been growing continuously in liquid culture for more than one year. JVM‐2 is characterized cytogenetically by t(11;14)(q13;q32), and JVM‐3 by trisomy 12. The immunoglobulin (Ig) heavy‐and light‐chain genes showed the same pattern of rearrangement in both lines as in the original prolymphocytes from each case. The cells from these lines showed a spectrum of morphological and immunological features corresponding to different stages of B‐cell maturation. The expression of Ig, IgM‐X in JVM‐2 and IgMD‐K in JVM‐3, changed from a predominantly membrane pattern in the original cells to a cytoplasmic one in the cell lines. By comparison with their original progenitors, the cells from both lines showed reduced reactivity with the monoclonal antibody (MAb) FMC7, and increased expression of the antigens recognized by the MAbs OKT10, α‐Tac, FMC53 and Ki‐I. The availability of cell lines from this rare type of lymphoid leukaemia offers a potential tool for the study of molecular events associated with the expression of Ig and other antigens by ncoplastic cells.
Seroepidemiologic survey of captive old‐world primates for antibodies to human and simian retroviruses, and isolation of a lentivirus from sooty mangabeys (Cercocebus atys)
Authors: Lowenstine Linda J. , Pedersen Niels C. , Higgins Joanne , Palus Katherine C. , Uyeda Ann , Marx Preston , Lerche Nicholas W. , Munn Robert J. , Gardner Murray B.
Published: February 2007

Sera from 526 Old‐World monkeys and apes, representing 50 species and 20 genera and living in US zoos and vivaria, were screened for antibodies to HTLV‐I, HTLV‐III/LAV, and simian‐AIDS retrovirus, type I (SRV‐I). Sera were screened initially by ELISA, and ELISA‐positive sera, as well as ELISA‐negative sera from cage contacts, were further tested by Western blotting. A large number of false‐positive and a small number of false‐negative ELISA sera were identified. Although most true positive reactions were directed to a single retrovirus, a number of individuals from 4 species were positive for more than one retrovirus. Specific seroreactivity to HTLV‐1 was found in 39/526 (7%) animals of 15 species. True positive reactions to SRV‐1 were found in 21/516 (4%) animals, including talapoins and 2 species of macaques. Specific serologic reactions to HTLV‐III/LAV were detected in 23/526 (4%) monkeys. Many of the HTLV‐III/LAV seropositive animals were from one mixed‐species zoo exhibit, containing sooty mangabeys, mandrills, Kolb's guenons, and talapoins. A type D virus was isolated from the blood of 3/10 SRV‐1 antibody‐positive Tonkeana macaques, but from none of 11 seropositive talapoins. A lentivirus was isolated from the blood of 4/7 HTLV‐III/LAV seropositive sooty mangabeys, but not from seropositive talapoins in the same exhibit or from 2 seropositive colobus from another zoo. The sooty mangabey lentivirus produced generalized lymphadenopathy, leukopenia, and decreased levels of T4 lymphocytes in 2 experimentally infected rhesus macaques.
Tumorigenicity of T lymphoma/T lymphoma hybrids and T lymphoma/normal cell hybrids
Authors: Hays Esther F. , Weinroth Stephen E. , Macleod Carol L. , Kitada Shinichi
Published: February 2007

Stable hybrids formed between clones of established murine T‐cell lymphoma lines, and between lymphoma clones and normal spleen or thymus cells were examined for their tumorigenic properties by intravenous (i.v.) and intradermal (i.d.) inoculation into syngeneic AKR mice. Fusion parents consisted of T lymphoma clones of high and low tumorigenicity derived from the SL 12 cell line. In addition, normal spleen cells and thymocytes were fused with poorly tumorigenic T‐lymphoma clones. Hybrids tested by i.v. inoculation of 106 cells to syngeneic hosts showed that fusion between the lymphoma cells resulted in hybrids which displayed the phenotype of the highly tumorigenic parent. Also, it was shown that fusion of poorly tumorigenic lymphoma cells with normal spleen cells resulted in hybrids with enhanced tumorigenicity. Fusion of poorly tumorigenic lymphoma cells with normal thymocytes resulted in hybrids with the highest tumorigenic potential. The pattern of spread for the tumor/tumor hybrid was that of the highly tumorigenic parent. Tumor spread patterns for the spleen/tumor hybrids were different from those of the thymocyte/tumor hybrids. Intradermal inoculation of 105 cells from tumor/spleen or tumor/thymocyte hybrids revealed differences in latent periods between parental and hybrid cells, the tumor/thymocyte hybrids having the shortest latent period. Surface marker studies and T‐cell antigen receptor mRNA determinations in the tumor cell/normal cell hybrids indicated that the normal parent was a cell of immature phenotype. Therefore, high tumorigenicity is a dominant characteristic, and poorly tumorigenic but “immortal” T lymphoma cells can derive characteristics which increase their In vivo growth capacity from the putative immature normal cells with which they selectively fuse.
Hras1‐selected, chromosome‐mediated transformants vary in phenotype in vitro and tumorigenic potential in vivo
Authors: Porteous D. J. , Morten J. E. N. , Foster M. E. , Cranston G. , Weir‐Thompson E. , Busuttil A. , Bostock C. J. , Steel C. M.
Published: February 2007

Transfection of mouse C127 cells with mitotic chromosomes isolated from a human EJ bladder carcinoma cell line gave rise, at high frequency, to foci of transformed cells. Independent, HRAS 1‐selected chromosome‐mediated transformants displayed distinctive cellular morphologies in monolayer culture and colony‐forming abilities in low‐melting‐point agarose. Subcutaneous inoculation of neonatally thymec‐tomized, Ara‐C‐protected, total‐body‐irradiated CBA mice was used to compare the tumorigenic potential of each transformant. Significant quantitative and qualitative differences in tumorigenicity were found between transformants which correlated with differences in malignant phenotype observed in vitro. The sensitivity of the tumorigenicity assay is such that rare transformation events can be selected directly in vivo.
Monoclonal antibody immunoradiometric assay for an antigenic determinant (CA 72) on a novel pancarcinoma antigen (TAG‐72)
Authors: Klug Thomas L. , Sattler Marcia A. , Colcher David , Schlom Jeffrey
Published: February 2007

CA 72 is a monoclonal antibody (MAb) ‐defined antigenic determinant expressed on a pancarcinoma antigen (TAG‐72) found in more than 85% of human colorectal carcinomas. An immunoradiometric assay has been developed using the murine MAb B72.3 to quantitate CA 72 in human serum. In a simultaneous immunoradiometric assay, the mean CA 72 concentration in 1,099 serum samples from healthy blood donors was 1.83±2.03 (SD) units/ml. If the upper limit of normal was set at 10 u/ml of serum, a value including 99% of healthy blood donors, only 4 of 101 serum samples (4%) from patients with benign disease were elevated, whereas 15 of 26 (58%) and 14 of 25 (56%) of rectal and colon carcinoma patient sera, respectively, were positive. Serum samples from 84 benign colorectal disease cases were examined; of these, 0 of 28 (0%) colorectal adenoma, 1 of 39 (3%) ulcerative proctocolitis, 0 of 15 (0%) diverticulosis, and 0 of 2 (0%) irritable bowel disease sera contained more than 10 u/ml CA 72. At a reference value of 20 u/ml, 0 of 101 (0%) benign disease and 2 of 1,060 (0.2%) blood donor sera had elevated values, whereas 10 of 26 (38%) and 9 of 25 (36%) rectal and colon patient sera, respectively, remained positive. The majority of patients with pancreatic and ovarian cancer, and a significant fraction of stomach cancer patient sera, also contained elevated levels of CA 72. The ability of this assay to discriminate between malignant and benign diseases suggests its further evaluation for monitoring and diagnosis in groups at risk for development of cancer.
Rearranged HPV 16 molecules in an anal and in a laryngeal carcinoma
Authors: Scheurlen Wolfram , Stremlau Armin , Gissmann Lutz , Höhn Dieter , Zenner Hans‐Peter , Hausen Harald Zur
Published: February 2007

By hybridization under stringent conditions, one out of two anal carcinomas and one out of 36 laryngeal carcinomas were shown to harbor HPV 16 DNA in high copy number. Further analysis of both tumor DNAs indicated a rearrangement of the viral DNA in the tumor cells. HPV 16 DNA in the anal carcinoma could chiefly be found episomally in two different forms: (1) a minority as 7.9‐kb oligomeric episomes with no apparent modifications; (2) as 10.7‐kb rearranged oligomeric episomes with a duplication of the part of the viral genome encoding the open reading frames (ORF) E7, E1 and parts of E6 and E2. In the laryngeal carcinoma, integrated and episomal HPV 16 DNA molecules of 7.9 kb were present, together with rearranged molecules of approximately 18 kb with multiple duplications of the ORF E4 and parts of the ORFs E2, E5, L1 and L2. Possible consequences for transcription of the modified viral genomes are discussed.
Tumour‐promoting effect of chilli extract in BALB/c mice
Authors: Agrawal R. C. , Wiessler M. , Hecker E. , Bhide S. V.
Published: February 2007

In 50% of BALB/c mice pretreated with atropine, tongue tumours were induced by fortnightly application of DMN‐OAc (2 mg/kg) on the tongue. When DMN‐OAc + TPA was used for the initiation‐promotion protocol, tumours were observed on the tongue, the site of application, in only 10% of animals. In the same group, stomach tumours were obtained in 63% of mice, denoting that initiation‐promotion could be successfully used to induce stomach tumours. Using a protocol of DMN‐OAc + chilli as a promoter, we observed induction of stomach tumours. The promoter effect of chilli extract was also seen in the BHC‐induced hepato‐carcinogenesis system. It thus appears that, in BALB/c mice, chilli acts as a promoter in stomach and liver carcinogenesis.
Adenomatous polyps and atherosclerosis: An autopsy study of Japanese men in Hawaii
Authors: Stemmermann G. N. , Heilbrun L. K. , Nomura A. , Yano K. , Hayashi T.
Published: February 2007

It is generally accepted that most colorectal cancers arise from adenomatous polyps and most coronary heart disease is caused by severe atherosclerosis. In order to compare the frequency of these disease precursors in men of Japanese ancestry in Hawaii, the degree of atherosclerosis of the aorta and coronary arteries was estimated by the panel method in 288 male autopsy subjects. The extent of atherosclerosis was then compared in men who did or did not have adenomatous polyps as determined at autopsy. The degree of atherosclerosis of the coronary arteries and aorta was positively and significantly related not only to the presence of adenomatous polyps, but to their size, multiplicity, and degree of atypia as well. This study suggests that shared environmental events could account for the development of severe atherosclerosis and adenomatous polyps. At the same time, it has been observed that Hawaii Japanese men experience colon and rectal cancer rates higher than those of US Whites, but their coronary heart disease (CHD) rates are intermediate between the low rates of Japan and the high rates of the US white population. These differences in disease trends and differences in the serum cholesterol and fat intake of Hawaii Japanese men with CHD and colon cancer have suggested that men with these diseases represent different subsets of the westernized Japanese population. If CHD and colon cancer occur in different subsets of this population, they must stem from the accumulation of other risk factors superimposed upon the initiators of their precursor lesions.
Antibodies to HTLV‐I in Nigerian blood‐donors, their relatives and patients with leukaemias, lymphomas and other diseases
Authors: Fleming A. F. , Maharajah R. , Abraham M. , Kulkarni A. G. , Bhusnurmath S. R. , Okpara R. A. , Williams Eka , Akinsete I. , Schneider J. , Bayer H. , Hunsmann G.
Published: February 2007

Antibodies to HTLV‐I have been detected in sera from 15 (2.0%) of 736 adult blood‐donors in Nigeria, in 4 (20.0%) of 20 patients with chronic lymphatic leukaemia, 3 (10.0%) of 30 with non‐Hodgkin's lymphoma, one of 12 with Burkitt's lymphoma and one of 7 with acute lymphoblastic leukaemia. The frequency of positivily was higher (3.6%) in the blood‐donors from the guinea and wooded savanna of northern Nigeria than in those from the rain‐forest and mangrove swamps of southern Nigeria (1.8% in Lagos and 0.7% in Calabar). Two of the 3 seropositive patients with lymphoma had clinical presentation and courses similar to those of Japanese and Caribbean patients with adult T‐cell leukaemia/lymphoma.
Non‐contraceptive oestrogens and the risk of breast cancer in women
Authors: La Vecchia Carlo , Decarli Adriano , Parazzini Fabio , Gentile Antonella , Liberati Cristina , Franceschi Silvia
Published: February 2007

The relationship between use of non‐contraceptive oestrogens and risk of breast cancer was investigated using data from a hospital‐based case‐control study from Northern Italy. This study covered 1,108 patients with histologically confirmed breast cancers and 1,281 control subjects with a large spectrum of acute conditions unrelated to any of the known or suspected risk factors for breast cancer. Compared with “never‐users”, the age‐adjusted relative risk for “ever‐users” was 1.93 (95% confidence interval = 1.35–2.75). The risk increased with duration of use (relative risk = 2.08 for over 2 years), but was unrelated to time elapsed since first or last use. Allowance for a large number of identified potential confounding factors, including indicators of socio‐economic status and the major determinants of breast cancer risk, failed to account for the observed association (multivariate relative risk = 1.84 for ever use and 2.04 for > 2 year use). Possible explanations for these findings and for their apparent discrepancy with some American data are discussed in terms of different baseline incidence of breast cancer in the two populations, and hence of potential baseline differences in availability of endogenous serum oestrogens. Nonetheless, the results of this study should be interpreted cautiously and viewed as a further contribution to a topic still open to debate.
Retinoblastoma cell differentiation in culture
Authors: Bogenmann Emil
Published: February 2007

Human retinoblastoma cells were grown in tissue culture and their differentiation into Flexner‐Wintersteiner rosettes was investigated. This process of photoreceptor cell differentiation was only observed in primary cultures and subsequent cell passages of tumors which showed these structures in vivo. Rosettes formed spontaneously within 5–9 d after plating of the tumor cells. Under optimal conditions in certain tumor cell strains, up to 80% of the cultured cell aggregates contained one or more differentiated Flexner‐Wintersteiner rosettes. Exposure of retinoblastoma cells to RA or dcAMP did not alter the number of rosettes in culture. Retinoblastoma cells within rosettes continued to synthesize DNA, and mitotic figures were frequently observed in histological sections. Ultrastructural analysis of rosettes formed in vitro showed many of the characteristics described in those found in vivo including a polarized shape, established cell junctions (Zonula adherens), extensive accumulation of mitochondria and microtubules in the apical part of the cells, numerous basal bodies and centrioles as well as cilia typical of the mature photoreceptor cell. Lamellated stacks of membranes were also found and their nature is discussed.
UICC multidisciplinary project on breast cancer. Management of early and advanced breast cancer
Authors: Hayward J. L. , Rubens R. D.
Published: February 2007

The purpose of the UICC Multidisciplinary Project was to determine strategies that might be adopted for prevention, detection and management of breast cancer and to define areas of general agreement and disagreement so that directions for future research might be defined. One particular aim was to determine what developments had occurred since the previous two meetings (Carter and Rubens, (1981). Canellos et al., (1982). This report summarizes the presentations, discussions and conclusions of the group, as perceived by the Rapporteurs. Although we believe it represents the consensus of the meeting, we alone are responsible for its accuracy.

The 21 participants reviewed predictive factors in early and advanced disease, options for treatment of the primary comples and the use of adjuvant therapy, both local and systemic. Particular attention was paid to the value of overview analyses. In the management of advanced disease, the use of systemic endocrine therapy and chemotherapy was also reviewed.
Immunological characterization of a novel human colon‐associated antigen (CAA) by a monoclonal antibody
Authors: Muraro R. , Wunderlich D. , Thor A. , Noguchi P. , Cunningham R. , Schlom J.
Published: February 2007

We have generated a monoclonal antibody (MAb), designated anti‐CAA (colon‐associated antigen), using as immunogen a membrane‐enriched fraction of a biopsy from a moderately‐differentiated human colonic adenocarcinoma. The molecular weight of this reactive antigen was determined by Western blotting to be greater than 200 kDa. When immunohistochemical techniques were used, MAb anti‐CAA reacted with epithelium in the majority of normal, dysplastic and malignant colon specimens tested (greater reactivity was observed in normal colon than in benign or malignant lesions). Cell sorter analyses demonstrated a heterogeneous distribution of CAA on the cell surface of the well‐differentiated LS‐174T cell line. Antigen positive and antigen‐negative cells were separated by means of flow cytometric techniques. These two subpopulations were then inoculated into immunosuppressed rats, resulting in xenograft tumors which differed significantly in their degree of histologic differentiation. Antigen‐positive cells developed into well‐differentiated adenocarcinomas, while antigen‐negative cells developed into poorly differentiated adenocarcinomas. These results, along with immunohistochemical studies, indicate that the antigen detected by MAb anti‐CAA has characteristics of a colon‐associated antigen whose expression correlates with cellular differentiation. Moreover, differences in molecular weight as well as tissue distribution indicate that CAA may be a novel antigen different from those previously described.
Quantitative and qualitative aspects of radiolocalization in colon cancer patients of intravenously administered MAb B72.3
Authors: Esteban J. M. , Colcher D. , Thor A. , Schlom J. , Sugarbaker P. , Reynolds J. C. , Carrasquillo J. A. , Larson S. M. , Bryant G.
Published: February 2007

Monoclonal antibody (MAb) B72.3 has been previously shown, by in vitro assays, to have a high degree of specificity for carcinomas of the colon, ovary and breast versus normal adult tissues. B72.3 IgG was labelled with 131I and injected i.v. into 20 patients with known or suspected colorectal cancer. All patients subsequently underwent surgical exploration, with tumor and selected normal tissues removed for staging purposes. The selective localization of 131I‐MAb B72.3 IgG was demonstrated in biodistribution studies in which the % ID/g of each tumor was compared with that of the normal tissues, thus providing a relative RI for each lesion. Of the tumor lesions, 70% (99/142) had an RI of at least 3 (i.e., 3 times greater uptake per gram than normal tissues), and 31% of the tumor lesions had RIs of over 10. Only 12 of 210 (6%) histologically normal tissues had RIs of > 3; either these tissues were adjacent to or draining tumor masses or, as in the case of 2 patients, the high RI values were apparently due to deposition of immune complexes in the splenic tissues. Several parameters were studied to determine factors that might influence MAb localization. Whereas tumors of all histologic types localized the MAb, 31% of the well‐differentiated mucinous carcinomas displayed tumor‐to‐normal ratios greater than 10, while less than 5% of the lesions of other tumor types demonstrated similar localization. The expression of the antigen (TAG‐72) detected by MAb B72.3 in these tumors, as studied by immunohistochemical techniques using tissue sections, did not always correlate with the outcome of the MAb distribution. No differences in MAb uptake were observed among the carcinoma lesions from numerous anatomic locations, demonstrating the ability of i.v. administered B72.3 to reach all the tumor sites. Furthermore, autoradiographic studies of tumors showed good penetration of the MAb into the medial areas of the tumors, regardless of their size.
Association of BK virus with human brain tumors and tumors of pancreatic islets
Authors: Corallini A. , Pagnani M. , Viadana P. , Silini E. , Barbanti‐Brodano G. , Mottes M. , Milanesi G. , Gerna G. , Vettor R. , Trapella G. , Silvani V. , Gaist G.
Published: February 2007

BK virus (BKV) DNA was detected by Southern blot hybridization in 19 out of 74 (25.6%) human brain tumors and in 4 out of 9 (44.4%) human tumors of pancreatic islets. BKV DNA was free, in an episomal state and generally in a low copy number (0.2 to 2 genome equivalents per cell). Only occasional tumors contained 10 to 20 genome copies per cell. Viral DNA sequences integrated into cellular DNA were not detected. A number of tumors expressed BKV‐specific RNA and T antigen. By transfection of total tumor DNA into human embryonic fibroblasts, viruses with the biological and antigenic properties of BKV were rescued from 6 brain tumors and from 2 tumors of pancreatic islets. Restriction endonuclease mapping of the genomes of the rescued viruses showed that they differ from wild‐type BKV. They are all similar to each other and to BKV‐IR, a virus previously rescued from a human tumor of pancreatic islets, suggesting the possible association of a BKV variant with specific types of human neoplasms. The significance of the relationship of these BKV variants to human tumors and their possible etiologic role in human oncogenesis are discussed.
Risk factors for cutaneous malignant melanoma in a northern italian population
Authors: Cristofolini Mario , Tasin Laura , Zumiani Giuseppe , Franceschi Silvia , Talamini Renato , Piscioli Francesco , La Vecchia Carlo
Published: February 2007

The relationship between cutaneous malignant melanoma (CMM) and the colour of skin, hair and eyes, the extent of sun exposure and reaction to it, education, and the occurrence of skin neoplasms in patients and their families was evaluated in a case‐control study of 103 cases of CMM and 205 control subjects hospitalized for acute conditions other than malignant or hormonal disease. A significantly higher risk was associated with fair skin as compared to dark/medium skin (RR = 4.0; 95% CI: 1.5‐10.5) and positive family history for CMM (RR = 8.1; 95% CI: 1.0‐200.9). CMM seemed to occur more frequently, but not significantly so, in individuals with brown or blond hair, higher education and clinically diagnosed dysplastic naevi. Outdoor occupation and heavy sun exposure in the last 20 years seemed to increase the risk of CMM in sunexposed sites but to be negatively associated with CMM in normally unexposed sites.
Non‐hodgkin's lymphoma and farming: An expanded case‐control study
Authors: Pearce Neil E. , Sheppard Raewyn A. , Smith Allan H. , Teague Clinton A.
Published: February 2007

A previously published case‐control study of agricultural risk factors involved male cases of non‐Hodgkin's lymphoma registered under code 202 of the International Classification of Diseases (ICD). This study has been expanded with the inclusion of cases registered under ICD code 200, and additional controls. The expanded study comprises 100 ICD 200 cases and 83 ICD 202 cases registered during the period 1977‐81, together with 338 controls selected from other cancer registrations during the same period. The largest relative risk for specific farming types was for orchard workers (odds ratio = 3.7, 90% confidence limits 1.1‐12.1). No elevated risks were observed for exposure to farm animals, nor for potential exposure to phenoxy herbicides (odds ratio = 1.0, 90% confidence limits 0.7‐1.5), or chlorophenols (odds ratio = 1.4, 90% confidence limits 0.8‐2.3). The previous finding of an excess risk associated with fencing work was weakly supported by the expanded study (odds ratio = 1.4, 90% confidence limits 1.0‐2.0). However, the previous finding of an excess risk associated with meat works employment was more strongly supported (odds ratio = 1.8, 90% confidence limits 1.2‐2.6). One relevant risk factor is 2,4,6‐TCP which is used in the treatment of pelts, but the excess risks do not appear to be confined to pelt department workers. An alternative hypothesis is that meat workers may be exposed to oncogenic viruses.
Genetic instability in fibroblasts of patients with thyroid cancers (TC)
Authors: Krizman D. B. , Pathak S. , Samaan N. A. , Hickey R. C.
Published: February 2007

In cultured fibroblasts initiated from fresh tumor biopsies of 11 patients with thyroid tumors, 5 medullary carcinoma of the thyroid (MCT) and 6 papillary follicular, the chromosomes are relatively unstable when compared with those from control fibroblast cultures. Tumor‐derived fibroblast samples showed a mean number of cells in metaphase with chromosome abnormalities at a frequency of 9.1% and a range of 6‐13%, whereas 5 controls exhibited a mean frequency of 4% and a range of 3‐5%. Our results indicate that genetic instability in thyroid cancer patients is present not only in peripheral blood cultures, as reported earlier, but in their fibroblast cultures as well.
Enhancement of production of superoxide anion by human monocytes exposed to products of ht 29 human colonic adenocarcinoma cell line
Authors: Bettetini Dominique , Garrouste Francoise , Remacle‐Bonnet Maryse , Culouscou Jean‐Michel , Pommier Gilbert , Marvaldi Jacques
Published: February 2007

The generation of superoxide anion (O2‐) by human blood monocytes in response to stimulation by either phorbol myristate acetate (PMA) or opsonized Zymosan was greatly enhanced (range: 100‐200% according to donor) by prior exposure of the peripheral blood mononuclear cells (PBM) to human colonic adenocarcinoma cells (HT 29 line) or their conditioned culture medium (DMEM‐HT 29). This priming effect was observed after 5 hr and persisted for up to 15 hr of contact between PBM and endotoxin‐free DMEM‐HT 29. Beyond this time, primed monocytes gradually lost this ability. However, they maintained a higher capacity (about 100%) to produce O2‐ when compared to controls. DMEM‐HT 29‐induced monocyte priming requires that the tumor‐active substance(s) act(s) on 2 target cells: first, on non adherent mononuclear cells (NA‐PBM) to induce cytokine production and, second, on the monocyte itself. Priming activity was also found in conditioned medium from FR3T3 embryonic fibroblasts but not in conditioned medium from HT 29 repolarized cells (by culture in glucose‐free medium) or from non‐tumorous human colonic mucosa explants.
Growth of a human colonic adenocarcinoma cell line (HT 29) on microcarrier beads: Metabolic studies by 31phosphorus nuclear magnetic resonance spectroscopy
Authors: Fantini Baetselier Jacques , Marvaldi Jacques , Galons Jean‐Philippe , Cozzone Patrick J. , Canioni Paul
Published: February 2007

A method allowing the growth of a human colon adenocarcinoma cell line (HT 29) on beaded polystyrene microcarriers has been developed by modifying the culture conditions used in monolayer cultures. Under optimized conditions, the cells became confluent 7 days after seeding and reached a density of 2.8 x 105 cells/cm of microcarrier (65% of the available area occupied). 31P NMR spectra were typically recorded on 300 x 106 cells continuously perfused at a flow rate of 15 ml/min in a specially designed NMR chamber in which the micro‐carrier beads were sequestered within the receiver coil volume. The in vivo spectrum displays a series of resonances assigned to nucleoside triphosphates (ATP and GTP), inorganic phosphate and various phosphomonoesters (mainly glucose‐6‐P and phosphorylcholine). Diphosphodiester resonances (DPDE, mainly UDP‐N‐acetyl‐glucosamine and UDP‐N‐acetylgalactosamine) were not detected in the in vivo spectrum and were only apparent in the spectrum of the perchloric acid extract of the cells, indicating that these compounds have a restricted mobility in the intracellular compartment. The intracellular pH of HT 29 cells was 7.2 during the perfusion with a medium buffered at pH 7.3. The internal pH decreased slowly (2 x 10‐3 pH unit/min) during anoxic perfusion, but severe intracellular acidosis occurred after 40 min of ischemia (2.7 x 10‐1 pH unit/min). Sequential recording of 31P NMR spectra has shown that HT 29 cells are able to maintain their high energy phosphorylated compound levels (ATP) when subjected to 100 min of anoxia and 40 min of total ischemia.
Growth of mammary epithelial cells in breast‐cancer biopsies correlates with egf binding
Authors: Spitzer Eva , Grosse Richard , Kunde Dieter , Eberhard Schmidt H.
Published: February 2007

In order to understand the role of EGF in the development of human mammary epithelial tissue, we analysed the binding of 125I‐EGF to sections of breast cancer biopsies. A mean specific 125I‐EGF binding of 8.9 fmol per mg protein was estimated in thin sections of 17 breast cancer biopsies. Microautoradiographic analysis of 125I‐EGF binding to the tissue sections was applied to demonstrate that EGF was bound predominantly to mammary epithelial cells. The binding was clearly correlated to the number of mitoses of mammary epithelial cells in the same samples. The highest EGF binding and proliferation rates were found in biopsies from breast cancer with axillary lymph‐node metastases.
Tumor type‐specific differences in cell‐substrate adhesion among human tumor cell lines
Authors: Varani James , McKeever Paul E. , Dixit Vishva , Carey Thomas E. , Flgiel Suzanne E. G.
Published: February 2007

Cell lines derived from human tumors of 4 different histological types (squamous carcinomas, melanomas, gliomas and a fibrosarcoma) were examined for cell‐substrate adhesion on plastic culture dishes and dishes coated with 50 μg of type‐IV collagen. In the absence of exogenous adhesion factors, the squamous carcinoma cells attached and spread more rapidly than the other cells on both substrates. Once attached, the squamous carcinoma cells were also more difficult than the other cells to remove with proteolytic enzymes/EDTA. While the cell lines derived from melanomas, gliomas and the fibrosarcoma were less adhesive than the squamous carcinoma lines in the absence of exogenous adhesion factors, these cells were highly responsive to laminin. In contrast, Iaminin only slightly enhanced the attachment and spreading of squamous carcinoma cells on the plastic dishes and actually inhibited attachment and spreading on the collagen‐coated dishes. These results indicate that there are tumor‐type‐specific differences in adhesiveness among human tumor cell lines and that cells from different tumor types may have distinct mechanisms for carrying out one of the functions critical to invasion.
In vitro antigenic modulation of human neuroblastoma cells induced by ifn‐γ, retinoic acid and dibutyryl cyclic amp
Authors: Gross N. , Beck D. , Favre S. , Carrel S.
Published: February 2007

Testing with a panel of 26 monoclonal antibodies (MAbs) showed the antigenic profile of 13 human neuroblastoma cell lines to be characterized by a generally poor antigenic expression; therefore, Interferon‐gamma (IFN‐γ), dibutyryl cyclic‐AMP and retinoic acid were used to analyse the modulation of surface antigenic expression during differentiation. Treatment of neuroblastoma cell lines with IFN‐γ resulted mainly in induction or increase of class‐I MHC antigenic expression. Induction of class‐II MHC antigens was obtained on only one neuroblastoma cell line out of 13, thus representing an exceptional event. An increase in some other antigens expressed by neuroblastoma cell lines was also observed. In contrast, and in addition to morphological maturation, treatment of these cell lines with the differentiation inducer dibutyryl‐cyclic‐AMP (dbc‐AMP), resulted in general down‐modulation of antigenic expression, particularly of neuroblastoma‐associated 5A7 or Leu7 antigens. Retinoic acid treatment had no significant effect on MHC antigens, but it decreased expression of 5A7 and Leu7 antigens, and markedly increased the expression of the melanoma‐associated antigen Me14‐D12. The similarity between the antigenic profile of in vitro differentiated neuroblastoma cells and that of mature ganglioneuroma cells suggests that compounds like cyclic‐AMP or retinoic acid are excellent tools for further investigations of the mechanisms of neuroblastoma differentiation and might have important clinical applications.
A monoclonal antibody (fmg25) that can differentiate neuroblastoma from other small round‐cell tumours of childhood
Authors: Gibson F. M. , Kemshead J. T.
Published: February 2007

The monoclonal antibody (MAb), FMG25, raised following immunization of mice with the human T cell line HUT 78, binds to human neuroblastoma but not to other small round‐cell tumours of childhood (rhabdomyosarcoma and Ewing's sarcoma). The specificity of the reagent is paralleled on normal tissues binding to brain but not frozen sections of thymus, tonsil, lymph node and spleen. Of the 15 T‐cell malignancies examined, only 3, belonging to the large T‐cell type, were positive. This represents only 50% of this type examined. Only one early case of pre‐B ALL was found to be positive for FMG25 binding out of 27 non‐T‐cell malignancies. The pattern of reactivity of FMG25 makes the MAb useful as a diagnostic reagent in paediatric pathology. In addition, the antibody may be useful as one of a panel of reagents applied to detect and remove tumour cells from bone marrow harvested for autologous transplantation.
Recurrent deletions of chromosomes 11q and 3p in anal canal carcinoma
Authors: Muleris Martine , Salmon Rémy‐Jacques , Girodet Jacques , Zafrani Brigitte , Dutrillaux Bernard
Published: February 2007

A cytogenetic study of 8 cases of anal canal cancer, including I cloacogenic and 7 squamous‐cell carcinomas, was performed. All tumors exhibited chromosomal abnormalities. A rearrangement involving the long arm of chromosome 11 was seen in all instances, and, with the exception of the i (11q) found in one tumor, all the observed rearrangements resulted in a deletion of the distal segment. Rearrangements of chromosome 3, detected in 6 tumors, led to a deletion of the short arm in 5 cases. The association of these 2 deletions may characterize the anal canal carcinoma, the smallest common deleted segments being distal to 11q22 or q23 and 3p22.
Suppression of transformed phenotypes in intraspecific somatic cell hybrid clones between the c‐myc activating mouse plasmacytoma line and normal cells
Authors: Oikawa Tsuneyuki , Kuzumaki Noboru , Yamada Toshiyuki , Chiba Itsuo , Yamagiwa Seiji
Published: February 2007

The role of normal‐cell‐derived chromosome 15 in suppressing transformed phenotypes was studied in intraspecific hybrid clones between the c‐myc oncogene activating BALB/c mouse plasmacytoma (S194) cells and normal spleen cells or fibroblasts from CBA/H‐T6 mice. All the hybrid clones between S194 and normal spleen cells grew very rapidly in suspension and formed colonies in soft agar. In contrast, the hybrid clones between S194 and normal fibroblasts grew slowly in an attached form. They were divided into 2 groups on the basis of their morphology and growth properties: most clones showed flat type morphology, and no colony formation was seen in soft agar, while some clones grew in a piled‐up fashion and formed colonies in soft agar. The hybrid clones between S194 and normal spleen cells lost some normal‐cell‐derived chromosomes but retained most tumor‐derived marker chromosomes including the t(12;15) chromosome which carried the activated c‐myc oncogene. On the other hand, hybrid clones between S194 cells and normal fibroblasts retained almost all chromosomes from both parental cells. With respect to retention of normal‐cell‐derived chromosome 15, both the flat and piled‐up type clones retained 2 copies each of the t(14;15) and T6 marker chromosomes, the normal counterparts of the t(12;15) chromosomes. Our results suggest that the transformed phenotypes of the hybrid clones between S194 cells and normal fibroblasts are negatively modulated by normal‐cell‐derived chromosomes but not by normal‐cell‐derived chromosome 15 alone.
Differential expression of endogenous sugar‐binding proteins (lectins) in murine tumor model systems with metastatic capacity
Authors: Gabius Hans‐J. , Bandlow Gert , Schirrmacher Volker , Nagel Gerd A. , Vehmeyer Katalin
Published: February 2007

In order to investigate possible differences in sugar binding activities of strongly versus weakly metastatic tumors, sugarbinding molecules (endogenous lectins) of murine tumor cells differing in metastatic capacity were analyzed by affinity chromatography on supports with immobilized sugars or glycoproteins and compared. After elution with specific sugar in the absence of Ca2+‐ions, the proteins were separated by sodium dodecyl sulfate‐polyacrylamide slab gel electrophoresis. In comparison to a weakly metastatic subline (Eb) spontaneous strongly metastatic variants (ESb) of a murine lymphoma contained additional sugar receptors for N‐acetylglucosamine (Mr 30 kDa) and maltose (Mr 64 kDa, 62 kDa, 54 kDa and 32 kDa), and lacked one sugar receptor for myoinositol (Mr 85 kDa), N‐acetylglucosamine (Mr 23 kDa) and maltose (Mr 22 kDa), respectively. The strongly metastatic variant ESb expressed the common β‐galactoside‐specific lectin to a higher extent and receptors for myo‐inositol, melibiose and mannan to a lower extent. In another model system derived from the murine mastocytoma cell line P 815 × 2A, biochemical analysis of the liver‐metastasizing variant P 815 × 2B revealed additional characteristic N‐acetylgalactos‐amine‐ and maltose‐specific binding proteins. This variant had reduced amounts of receptors for β‐galactosides and fucose in comparison to the parental clone. In a third tumor system a similar qualitative difference was disclosed: a metastatic variant derived from spleen metastases displayed a sugar receptor profile with 5 additional β‐galactoside‐binding proteins when compared to its parental clone 6‐6#3 + F, which is a virally transformed fibroblast line. The results show that metastatic variants of 3 murine tumor models consisting of lymphomas, mastocytomas and sarcomas are characterized by qualitative and quantitative alterations in the profiles of sugar‐binding proteins.
Presence of in vivo‐activated t‐cells expressing hla‐dr molecules and il‐2 receptors in peripheral blood of patients with nasopharyngeal carcinoma
Authors: Lakhdar M. , Ellouz R. , Kammoun H. , Ben H'Tira S. , Khedhiri N. , Kastally R. , Fridman W. H.
Published: February 2007

Epstein‐Barr Virus (EBV) is associated with two malignant diseases, African Burkitt's Lymphoma (BL) and Undifferentiated Nasopharyngeal Carcinoma (UNPC). North Africa is a geographical area with a high incidence of NPC. Our purpose in this study was to explore cell‐mediated immunity of peripheral blood lymphocytes (PBL) from patients with UNPC and DNPC. We found an elevated percentage of OKT8 cells and of large granular lymphocytes (LGL) (30 ‐ 35% HNK‐I‐positive cells) compared to PBL from healthy matched individuals. PBL from NPC patients contained 35% HLA‐DR‐ positive and 30% Interleukin‐2 (IL‐2) receptor‐positive circulating lymphocytes. PBL from NPC patients exhibited a normal proliferative response to phytohemagglutinin (PHA) and Concanavalin A (Con A) and an increased response to pokeweed mitogen (PWM). Natural killer (NK) activity towards K562 cells was low in our patients who, in addition, exhibited no lytic activity against HLA‐matched EBV‐transformed B cells. This lack of cytotoxicity against an EBV‐transformed B‐cell line cannot be explained by an impairment of IL‐2 secretion, and is probably a result of the presence of high numbers of OKT8 suppressor T cells.