bluuebunny/crossref_metadata_2025 huggingface dataset:
Disseminated or localized growth of a human B‐cell tumor (Daudi) in scid mice
Authors: Ghetie Maria‐Ana , Richardson James , Tucker Thomas , Jones Diane , Uhr Jonathan W. , Vitetta Ellen S.
Published: February 2007

A human Burkitt lymphoma (Daudi) has been grown in the mutant mouse called C.B‐17 SCID. Twenty‐eight days after s.c. injection of Daudi cells, a palpable tumor grew only at the site of injection in all injected mice. In contrast, after intravenous (i.v.) or intraperitoneal (i.p.) injection, macroscopic, disseminated tumors developed. Following i.v. inoculation, tumors grew in the lungs, kidneys, ovaries and adipose tissue, and microscopic tumor infiltrates were observed in the spleen, bone marrow, spinal column and femur, whereas after i.p. injection, the tumors were localized in the abdomen, liver, spieen, ovaries and muscular tunics of the gut, but did not disseminate into the lung or bone marrow. The growth pattern and phenotype of the Daudi cells were similar whether the inoculated tumor cells were derived from the in vitro cell line or from in vivo passaged tumors. The survival time of the tumor‐bearing animals was dependent on the dose of i.v.‐administered Daudi cells; as few as 100 cells caused death. All mice injected i.v. showed paresis or paralysis of the hind legs just prior to death. This was associated with the presence of neoplastic nodules within the spinal canal. Two surface antigens on Daudi cells (CD19 and CD22) were stably expressed in all the neoplastic lesions. Radiolabelled anti‐CD22 antibodies localized in organs infiltrated with tumor, but did not penetrate primary s.c. tumors.

This model of disseminated vs. solid tumor should prove useful for evaluating the efficacy of different types and doses of therapeutic antibodies, immunoconjugates and immunotoxins prepared from anti‐human B‐cell antibodies.
Aspergillus species strain m39 produces two naphtho‐γ‐pyrones that reverse drug resistance in human KB cells
Authors: Ikeda Shun‐Ichi , Sugita Masanori , Yoshimura Akihiko , Sumizawa Tomoyuki , Douzono Haruhiko , Nagata Yukihiro , Akiyama Shin‐Ichi
Published: February 2007

One thousand fungi and Actinomycetes were investigated to see whether they produced compounds that reverse multidrug resistance in KB cells. Only one Aspergillus strain M39 produced agents with resistance‐reversing activity and these compounds were identified to be rubrofusarin B and dianhydro‐aurasperone C. Rubrofusarin B only slightly reversed the resistance of KB‐C2 cells to Adriamycin and daunomycin, partially reversed the resistance to chromomycin A3, and almost completely reversed the resistance to vincristine and mitomycin C. Purified dianhydro‐aurasperone C and rubrofusarin B had similar effects on drug resistance in KB‐8‐5 cells. Dianhydro‐aurasperone C enhanced the accumulation of vinblastine in KB‐8‐5 cells and inhibited the efflux of vinblastine from the cells. Dianhydro‐aurasperone C and rubrofusarin B at 10 μ M completely inhibited 3H‐azidopine photolabelling of P‐glycoprotein. The two products of Aspergillus strain M39 appear to reverse multi‐drug resistance by interacting with P‐glycoprotein and inhibiting its role as an active efflux pump.
Differences in C‐myc and pvt‐1 amplification in sewa sarcoma sublines selected for adherent or non‐adherent growth
Authors: Minarovits Janos , Steinitz Michael , Boldog Ferenc , Imreh Stephan , Wirschubsky Zvi , Ingvarsson Sigurdur , Hedenskog Mona , Minarovits‐Kormuta Susanna , Klein George
Published: February 2007

Conversion of solid sarcomas and carcinomas into ascites tumors depends on the in vivo selection of phenotypically altered tumor cell variants that can grow in the dissociated form. Once selected, they retain this property even after prolonged s.c. growth as solid tumors. From an s.c.‐passaged subline of an ascites‐converted murine sarcoma (SEWA‐AS12), we were able to separate cells adapted to the ascites form of growth from cells that can only grow in the solid form on the basis of their differential adherence to plastic. Both c‐myc and pvt‐1 were amplified approximately 63‐ to 77‐fold in the nonadherent subline (SEWA‐AS12‐NA), but only 5‐ to 8‐fold in the adherent subine (SEWA‐AS12‐ADH). This suggests that c‐myc and/or pvt‐1 amplification may provide a selective advantage to cells that can grow in the dissociated form.
Del cell line: A “malignant histiocytosis” CD30 + T(5;6)(Q35;P21) cell line
Authors: Barbey Sylvette , Gogusev Jean , Mouly Héléne , Le Pelletier Odile , Smith Wandy , Richard Stephane , Soulie Joëlle , Nezelof Christian
Published: February 2007

A new cell line DEL, established in vitro, was isolated from a pleural effusion of a boy who died of malignant histiocytosis. Its principal characteristics are: strong positivity with monoclonal antibodies (MAbs) to CD25, CD30, CD45R, KiM7, EMA, HLA CI I and II; constant presence of acid phosphatase, ANAE, α‐anti‐trypsin, α‐anti‐chymotrypsin and NBT reduc‐tase activity; rearrangement of the immunoglobulin heavychain gene (JH) and a germ‐line configuration of the T‐chain gene; and finally a translocation between chromosomes 5–6 with a breakpoint in 5q35. The DEL cell line is appropriate for studying the role of the 5q localized c‐fms oncogene and of the genes of the mononuclear phagocyte growth factor (CSFI) and of their receptors in the dynamics and etiology of malignant hemopathies associated with a 5q35 breakpoint.
Further characterization, isolation and identification of the epithelial cell‐surface antigen defined by monoclonal antibody aua1
Authors: Durbin H. , Rodrigues N. , Bodmer W. F.
Published: February 2007

The human epithelial antigen recognized by monoclonal antibody (MAb) AUAl has been characterized as a cell‐surface glycoprotein. It has been isolated from human colonic mucosa by AUAl affinity separation. N‐terminal peptide sequence of this purified material has revealed a 17 amino acid sequence which identifies it with one of a group of similar epithelial/tumour‐associated glycoproteins defined by a variety of MAbs. Using the polymerase chain reaction to map the gene encoding this antigen, our previous AUAl antigen assignment to chromosome 2 has been confirmed.
Dietary factors and risk of pancreatic cancer: Results of a Canadian population‐based case‐control study
Authors: Howe G. R. , Jain M. , Miller A. B.
Published: February 2007

Dietary information from a case‐control study of pancreatic cancer conducted in Metropolitan Toronto between 1983 and 1986 is reported. A total of 249 cases and 505 populationbased controls completed quantitative diet histories from which total caloric intake and the intake of a number of nutrients were estimated. A positive association with total caloric intake was observed with a relative risk of 2.39, 95% confidence interval 1.18–4.83 (highest versus lowest quartile), due primarily to the intake of carbohydrates. Inverse associations were seen with fibre from fruit, vegetable and cereal sources, with a relative of risk of 0.42, 0.22–0.78 (highest versus lowest quartile), for total fibre intake.
Cancer in Jewish migrants to Israel
Authors: Parkin D. M. , Steinitz R. , Khlat M. , Kaldor J. , Katz L. , Young J.
Published: February 2007

Data on the incidence of 15 cancers in the Jewish population of Israel from the period 1961–1981 have been studied with emphasis on the risk of disease in relation to birthplace, calendar time, and duration of residence in Israel. The results show wide variations in incidence by birthplace, from less than 2‐fold for pancreatic cancer to a 40‐fold difference for oesophageal cancer in females; the reasons for these are often little understood. The potential importance of environmental agents in aetiology for different migrant groups is discussed in relation to the size and rapidity of changes in risk related to the duration of residence in Israel.
Expression of the mdr3 gene in prolymphocytic leukemia: Association with cyclosporin‐a‐induced increase in drug accumulation
Authors: Nooter Kees , Sonneveld Pieter , Janssen Arjenne , Oostrum Robert , Boersma Ton , Herweijer Hans , Valerjo Dinko , Hagemeijer Anne , Baas Frank
Published: February 2007

Typical multidrug resistance in human and animal cell lines is caused by overactivity of an unidirectional transmembrane drug efflux pump, encoded by the MDR genes, called mdr genes in mice and humans and pgp genes in hamsters. In humans, two mdr genes, mdr1 and mdr3, with approximately 80% nucleotide homology, have been identified. There is increasing evidence that overexpression of the mdr1 gene plays a role in resistance to anticancer agents in specific tumor types. However, currently no data are available on a possible role for mdr3 in drug resistance. Here we report high levels of expression of mdr3 gene sequences in leukemic cells from 6 out of 6 patients with prolymphocytic leukemia (PLL). No mdr1 expression was detected in 5 out of 6 of these samples, whereas a low level of mdr1 expression was found in a sample from one PLL patient in the course of transformation to non‐Hodgkin's lymphoma. Except for this patient, all other PLL cases studied had not received prior chemotherapy. In vitro drug uptake studies showed that daunorubicin accumulation in PLL cells was increased by cyclosporin A. Since cyclosporin A is an inhibitor of the mdr1‐encoded P‐glycoprotein drug pump, these data suggest that in PLL cells mdr3 also codes for a drug efflux pump. Our findings could partly explain the primary refractoriness of PLL to chemotherapy.
Malignant lymphoma of the central nervous system in Japan: Histologic and immunohistologic studies
Authors: Aozasa Katsuyuki , Ohsawa Masahiko , Yamabe Hirohiko , Shima Nobuko , Kirimoto Koji , Yamane Tetsumi , Tsujimoto Masahiko , Kobayashi Yasushi , Kurata Akihiko , Osada Hiromi , Konishi Fumio , Nagashima Kazuo
Published: February 2007

Ninety‐seven Japanese patients with so‐called primary non‐Hodgkin's lymphoma of the central nervous system (CNS‐NHL), unrelated to the acquired immunodeficiency syndrome (AIDS) or organ transplantation, were reviewed. The patients' ages ranged from 1 to 87 years (median: 58 years) with a male to female ratio of 1.77:1. The most frequent past histories were acute appendicitis (appendectomy), head injury, uveitis or iritis, and gastritis or gastric ulcer. These patients presented with symptoms suggesting an expanding intracranial lesion with no signs of extracranial lymphomatous disease. Combined computed tomographic scans, angiography, and findings at surgery or autopsy showed that the cerebrum was the commonest site of involvement, 87% of all cases, with the frontal to temporal region being the most commonly involved. Histologically, the diffuse large‐cell type was most frequent and 26% of lymphomas were of high‐grade malignancy as defined by the Working Formulation. The reported frequency of high‐grade CNS‐NHLs in AIDS patients in the United States is much higher (over 60%). Immunohistochemistry on paraffin‐embedded sections revealed a B‐cell nature of the present series of tumors. In 16% of the cases, large numbers of small lymphoid cells with a positive reaction predominantly for anti‐T lymphocyte antibodies surrounded the tumors or aggregated around the capillaries. The tumors which were infiltrated by small lymphoid cells showed more favorable prognosis than those which were not, suggesting a host reaction to tumor growth in these patients.
Risk factors for male breast cancer: A Franco‐Swiss case‐control study
Authors: Lenfant‐Pejovic Marie‐Hélène , Mlika‐Cabanne Najoua , Bouchardy Christine , Auquier Ariane
Published: February 2007

In order to evaluate risk factors in male breast cancer, a case‐control study of 91 histologically diagnosed cases and 255 cancer controls, matched for age and year of diagnosis, was conducted in Villejuif (France) and Geneva (Switzerland). Factors studied included marital history, occupational exposure, associated diseases, family history of breast cancer, history of radiation exposure and drugs which increase or are suspected of increasing prolactin or estrogen levels. Cases were significantly more likely to be bachelors or to work as butchers than were the controls. Other statistically significant risk factors identified were family history of breast cancer and therapeutic use of digitalis. Elevated risks, although not significant, were observed for individuals with a past history of tuberculosis, hyperthyroidism, liver cirrhosis or gallstone, who had been treated with isoniazid, or who had worked in high environmental temperatures. Further studies are needed to confirm our results particularly as regards hormonal imbalance and genetic factors.
Cancer in Mali, 1987–1988
Authors: Bayo Siné , Parkin Donald Maxwell , Koumaré A. K. , Diallo A. N. , Ba T. , Soumaré S. , Sangaré S.
Published: February 2007

Results from the population cancer registry in Bamako, Mali, for the years 1987 and 1988, are presented. The age‐standardized incidence for all cancers is high compared with rates reported elsewhere in West Africa (119.6 per 105 in males and 88.3 per 105 in females), but the leading cancers in each sex are the same (liver cancer in males, cervix cancer in females). The incidence of stomach cancer is the highest recorded in Africa, while rates for lung cancer, although low, exceed those in earlier series from registries in the region.
Alpha1‐antitrypsin and survival in pancreatic cancer
Authors: Trichopoulos Dimitrios , Tzonou Anastasia , Kalapothaki Victoria , Sparos Loucas , Kremastinou Tzenny , Skoutari Maria
Published: February 2007

The association between serum levels of alpha1‐antitrypsin (a1AT) at the time of diagnosis and survival was studied in a group of 44 patients with confirmed pancreas cancer. All 44 patients were followed until time of death, which occurred in all cases from pancreas cancer, with a median time of 3 months and a range of 0.5 to 16 months. Cox's proportional hazards model was utilized in the analysis controlling for sex, age and tobacco smoking. Males, older patients and smokers have higher fatality rates, but none of these relations was statistically significant. By contrast, there was a statistically highly significant association of increased levels of serum a1AT, at the time of diagnosis of the cancer of pancreas, with shorter survival; patients with serum a1AT higher by 100mg/100ml had a 57% higher fatality rate. These results indicate that serum a1AT represents a clinically interesting prognostic factor in pancreas cancer.
Fucose and galactose receptor and liver recognition by lymphoma cells
Authors: Vavasseur F. , Berrada A. , Heuze F. , Jotereau F. , Meflah K.
Published: February 2007

A syngeneic model system for the study of metastases is described. The system consisted of 2 lymphoma clones (A/63‐1 and A/63‐2) derived from a single thymoma (A/63) induced by a wild‐type Abelson‐Moloney viral complex. Phenotype and genotype analyses revealed that both clones were derived from transformation of early T‐cell precursors. An in vivo study of the colonizing potential following intravenous (i.v.) injection of clones showed that only the A/63‐1 cell clone colonized the liver. This observation was confirmed by quantitative analysis of organ distribution of both cell clones consecutive to i.v. injection of 125IUdR‐labelled cells. In the same way, an in vitro study of the invasive potential of both clones was performed on frozen liver sections and showed that only the A/63‐1 cell clone had the ability to attach to liver. This specific adhesion was inhibited by L‐fucose, D‐galactose, N‐acetyl‐D‐galactosamine (D‐GalNAc) and with D‐galactose‐and L‐fucose‐containing neoglycoproteins. Differences in cell surface carbohydrates of the 2 cell clones were detected using various lectins: peanut agglutinin (PNA), Dolichos biflorus (DBA), Aleuria aurantia (AAA) and Galactia tenuiflora agglutinins (GTA). A/63‐1 was found to react strongly with PNA, DBA and GTA, and the removal of sialic acid by neuraminidase treatment increased DBA and PNA receptor sites of A/63‐2 as compared to A/63‐1. The present data suggest that cell‐surface GalNAc, galactosyl and fucosyl residues are responsible for the ability of the A/63‐1 cell clone to recognize liver tissue probably through binding to a Kupffer‐cell‐associated lectin.
Establishment of immortalized primate epithelial cells with sub‐genomic EBV DNA
Authors: Karran Loraine , Teo Chong Gee , King David , Hitt Mary M. , Gao Yanning , Wedderburn Nina , Griffin Beverly E.
Published: February 2007

The genetic information in a sub‐fragment of EBV DNA, designated p31 (containing less than a quarter of the viral genome and derived from a recombinant DNA cosmid library) allows epithelial cells from primary monkey and human kidney cultures to escape senescence under standard tissue culture conditions. A number of epithelial cell lines, designated M1/31, 483/31, 199/31 and HK/31, have been established and characterized following transfection of primary cells with p31 DNA. They share many properties, although morphologically they are not all identical. The cultures are immortalized but not fully transformed or tumorigenic. They appear to be phenotypically stable, although DNA hybridization studies indicate that genotypic alterations, including amplification, occur subsequent to transfection with p31 DNA and the establishment of a continuously proliferating epithelium. All cell lines consistently express high levels of cytokeratin 18 and varying amounts of cytokeratin 7, demonstrating their epithelial origin. From a single marmoset kidney (designated 199) a series of related immortalized cells, with subtle phenotypic differences, have been generated by p31 or sub‐fragments of it. Although hallmarks of a “hit‐and‐run” mechanism are apparent in all of our studies, 2 different techniques (in situ hybridization or selection for cell survival in semi‐solid media, followed by nucleic acid hybridization) show that, in late‐passaged cultures, a small proportion of the cells still contain some viral DNA. The studies focus on genetic information within the BamHI A and I regions as being relevant to immortalization. The role of the EBV DNA fragment in the genesis of epithelial cell lines is considered.
Identification of T‐cell antigens expressed by metastatic T‐cell hybridomas and lymphomas
Authors: Van Hecke Dominique , Verschueren Hendrik , De Baetselier Patrick
Published: February 2007

Using the murine BW5147 tumor model system, we have identified 3 MAbs that discriminate between metastatic and non‐metastatic BW5147‐derived T‐cell hybridomas and BW5147‐unrelated T‐lymphomas. The 3 rat MAbs appear to recognize an identical membrane‐associated sialoglycoprotein with an approximate molecular weight of 95–100 kDa. We thus defined “metastatic T‐cell hybridoma” antigens (MTH‐Ags) that are also expressed on normal T‐lymphocytes. No correlation was found between the expression of the MTH Ags and in vitro invasive behavior of normal and malignant cells. Neither did we find any relationship between organ specificity of i.v. inoculated tumor cells and their MTH‐Ags expression. It thus remains unclear whether our MTH‐Ags are functionally involved in the metastatic process, or whether their expression is only incidentally related to the metastatic potential.
Serum CEA and CA 19‐9: Potential future diagnostic or screening tests for gallbladder cancer?
Authors: Strom Brian L. , Maislin Greg , West Suzanne L. , Atkinson Barbara , Herlyn Meenhard , Saul Scott , Rodriguez‐Martinez Hector A. , Rios‐Dalenz Jaime , Iliopoulos Dimitrios , Soloway Roger D.
Published: February 2007

The poor prognosis of gallbladder cancer and the presence of high‐risk populations make the identification of a screening test for this disease very desirable. As part of an ongoing case‐control study of gallbladder cancer being conducted in Mexico City, Mexico, and in La Paz, Bolivia, blood specimens were sought from all patients with cancer of the gallbladder and on controls of similar age and sex undergoing upper abdominal surgery. Each sample was analyzed for carcinoembryonic antigen (CEA) and CA 19‐9. Using the specimens from Bolivia, a serum CEA cutoff of 4.0 ng/ml yielded a sensitivity of 50.0% and a specificity of 92.7%, while a serum CA 19‐9 cutoff of 20.0 units/ml yielded a sensitivity of 79.4% and a specificity of 79.2%. Using ROC curve analysis, the latter was a much better test than the former (p < 0.05). Using the tests in series or in parallel did not substantively improve the results. The specimens from Mexico were used for validation purposes, and yielded very similar results. In conclusion, serum CA 19‐9 and CEA are fairly good tests for discriminating patients with gallbladder cancer from patients with gallstones and no cancer, the former being a better test than the latter. These tests may be useful in identifying disease recurrences. In addition, if a sufficiently high‐risk population could be identified, this could potentially become a useful screening test for this serious disease, allowing early intervention. However, additional data are needed prior to recommending this clinically.
The seroepidemiology of human herpesvirus‐6 (HHV‐6) from a case‐control study of leukaemia and lymphoma
Authors: Clark D. A. , Alexander F. E. , McKinney P. A. , Roberts B. E. , O'Brien C. , Jarrett R. F. , Cartwright R. A. , Onions D. E.
Published: February 2007

Sera from an epidemiological case‐control study of leukaemias and lymphomas conducted between 1980 and 1986 were examined for reactivity to human herpesvirus‐6 (HHV‐6) by an indirect immunofluorescence assay. Statistical analyses of the data revealed higher HHV‐6 seroprevalence and antibody titres in the cases, particularly evident in the disease subtypes acute myeloid leukaemia, Hodgkin's disease (HD), and low‐grade non‐Hodgkin's lymphoma. Within the control group alone, HHV‐6 seroprevalence was placed at 55% at a serum dilution of 1:40. The controls also displayed higher seropositivity in females as compared with males. Further analyses suggest an association of increased HHV‐6 seropositivity and geometric mean titre ratio with HD among young adults lacking social contact in the family group. This finding might indicate late exposure to HHV‐6 in such persons and could possibly signify late exposure to a number of viruses, including those hypothesized as playing a role in the aetiology of HD. Previous reports have nominated Epstein‐Barr virus as a possible candidate. Our results suggest that HHV‐6 should be included in further investigations of the aetiology of HD.
Tumor‐specific T‐cell clones recognize different protein determinants of autologous human malignant melanoma cells
Authors: Notter Michael , Schirrmacher Volker
Published: February 2007

This study attempts to characterize human melanomaassociated tumor antigens that are recognized by autologous T‐lymphocyte clones. Peripheral blood lymphocytes of a melanoma patient (AV) were activated in an autologous‐mixedlymphocyte tumor culture (AMLTC) and responding cells were cloned using irradiated autologous melanoma cells (AV‐Mel) as antigen source, EBV‐transformed B‐lymphoblasts as feeder cells and recombinant Interleukin 2. T‐cell clones were isolated which proliferated in response to autologous tumor cells, but not to autologous B‐lymphoblasts (AV‐B), and which were cytolytic for AV‐Mel cells. In an attempt to identify the antigens recognized, an in vitro test system was used, in which 3H‐Thymidine (3H‐TdR) incorporation by T lymphocytes was measured in the presence of protein from AV‐Mel cells presented by irradiated autologous accessory cells. Antigenbearing particles of AV‐Mel or AV‐B cells were prepared by spotting cell lysates onto nitrocellulose (NC) followed by dissolution with DMSO and precipitation with an aqueous buffer. T cells sensitized against autologous melanoma cells were specifically stimulated by NC‐bound AV‐Mel protein. Stimulation required the presence of AV‐B accessory cells, indicating that B‐lymphoblasts are able to present tumor antigens. This approach facilitates screening of polypeptide fractions of AV‐Mel cells separated by polyacrylamide gel electrophoresis followed by Western blotting for their capacity to stimulate antigen‐dependent T‐cells. CD4+ and CD8+ tumorspecific clones appear to recognize different antigens on the tumor cell: proliferation of an antigen‐dependent CD8+ clone was stimulated by 240‐ and 24‐kDa protein fractions, while proliferation of 2 antigen‐dependent CD4+ clones was observed either with an 84‐ or with 140‐ and 55‐kDa fractions. Molecular definition of the different antigens of tumor cells recognized by autologous T cells may be a prerequisite in attempts to manipulate T‐cell‐mediated anti‐tumor responses in a controlled way.
Variations in the uptake of beta‐carotene in the oral mucosa of individuals after 3 days of supplementation
Authors: Gilbert Ann‐Marie , Stich Hans F. , Rosin Miriam P. , Davison Allan J.
Published: February 2007

Variations in the response of individuals to beta‐carotene supplementation were studied by measuring the accumulation of beta‐carotene in oral mucosa cells. Beta‐carotene was administered orally to 178 individuals for 3 consecutive days, exfoliated oral mucosa cells were collected by brushing the entire oral mucosa on the 7th day following supplementation, and the beta‐carotene content was measured by HPLC analysis of the pronase‐treated cells. The rise in beta‐carotene levels in the oral mucosa following supplementation varied considerably. Significant differences in mean beta‐carotene levels in the oral mucosa were observed in 4 population groups. After supplementation, beta‐carotene levels increased by factors of 10.3 (100 Mile House), 7.8 (Williams Lake), 6.9 (Lytton) and 3.4 (Vancouver), respectively. This difference in mean beta‐carotene values is due to there being different proportions of weak and strong responders in the various population groups. Neither peak levels nor increases in beta‐carotene levels were correlated with base‐line concentrations of beta‐carotene in the pre‐supplementation samples. A second supplementation was given to 54 individuals several months after the initial supplementation. Of 17 weak responders in the first supplementation study, 10 (58.8%) individuals again showed only a small increase. A time‐course study revealed that low responders showed no significant changes in beta‐carotene levels over the 21 days following supplementation. Particular attention should be paid to weak responders when results of intervention trials using betacarotene are interpreted.
Detection of antibodies to human T‐lymphotropic virus type I by using synthetic peptides
Authors: Kuroda Naotaka , Washitani Yukiko , Shiraki Hiroshi , Kiyokawa Hiroyuki , Ohno Motonori , Sato Hiroyuki , Maeda Yoshiaki
Published: February 2007

We describe an enzyme‐linked immunosorbent assay (ELISA) for antibodies to HTLV‐1 using synthetic peptides corresponding to antigenic regions of HTLV‐1 structural protein. We observed that the peptides amino acid 100–119, 100–130, 131–160 and 295–314 of the gag protein, and 89–115, 175–199, 350–386 and 458–488 on the env protein correspond to the antigenic regions of HTLV‐1 structural protein. In particular, the peptide corresponding to amino acid 100–130 of the gag protein reacted with antibodies in all sera from HTLV‐1 carriers diagnosed by particle agglutination assay (PA) and indirect immunofluorescence assay (IF), but did not react with sera from healthy volunteers judged to be negative by PA and IF. Our results indicate that the ELISA using the peptide 100–130 of the gag protein can be used for donor screening of HTLV‐1 antibodies.
Tobacco and alcohol as risk factors in cancer of the larynx in Kerala, India
Authors: Sankaranarayanan R. , Duffy Stephen W. , Nair M. Krishnan , Padmakumary G. , Day Nicholas E.
Published: February 2007

A case‐control study of cancer of the larynx was carried out in Kerala, Southern India, on 191 male cancer cases and 549 male hospital‐based controls. Risk factors investigated were pan(betel)‐tobacco chewing, bidi and cigarette smoking, drinking alcohol and inhaling snuff. Significant positive associations with risk were observed for bidi smoking (p < 0.001), bidi and cigarette smoking (p < 0.001) and drinking alcohol (p < 0.001). A predisposing effect of smoking cigarettes alone approached significance (0.1 < p < 0.05), What appeared to be an almost significant protective effect of pan‐tobacco chewing (0.1 < p < 0.05) was found to be an artefact of confounding with smoking, and indeed a significant predisposing effect was observed of occasional chewing (p < 0.001). After a stepwise logistic regression to eliminate those factors which were not significant when adjusted for other factors, significant effects remained of durations of bidi smoking and cigarette smoking, daily frequency of bidi and cigarette smoking and duration of alcohol drinking. Relative risks of 7.12, 5.18 and 2.58 were observed for durations of more than 20 years of bidi smoking, cigarette smoking and drinking alcohol respectively, and a relative risk of 12.68 was observed for those smoking more than 20 bidis/cigarettes per day, in each case relative to a baseline of those negative for the relevant habit.
Aids‐related B‐cell non‐Hodgkin's lymphomas in direct blood‐stream HIV‐infected patients: Pathogenesis and differentiation features
Authors: Boiocchi M. , Carbone A. , De Re V. , Dolcetti R. , Volpe R. , Tirelli U.
Published: February 2007

Six AIDS‐related NHLs from direct blood‐stream HIV‐infected patients were characterized for clonality, maturation cell characteristics, activation of c‐myc proto‐oncogene and presence of HIV and EBV genomes. Four out of the 6 AIDS‐related NHLs were of immature B‐cell origin, contrasting with the lower frequency (2 out of 31) of immature B‐cell NHLs occurring in HIV‐negative patients. Moreover, 3 out of the 4 AIDS‐related pre‐B‐NHLs were extranodal lymphomas. C‐myc translocations or rearrangements were not found in Italian AIDS‐related NHLs, unlike c‐myc activation which had a high prevalence in the American series of AIDS‐related NHLs. HIV and EBV are not, or only occasionally, directly involved in AIDS‐related NHL pathogenesis since HIV genome has never been found in the neoplastic clones and EBV genome was detected in only 1 out of the 6 lymphomas analyzed.
Deficiency in catalase activity correlates with the appearance of tumor phenotype in human keratinocytes
Authors: Rabilloud Thierry , Asselineau Daniel , Miquel Corinne , Calvayrac Regis , Darmon Michel , Vuillaume Monique
Published: February 2007

Biopsies isolated from various human stratified epitheliomas and cultures of the associated fibroblasts exhibit a break‐down in catalase activity (70 to 95%). We report here that primary human cultures of keratinocytes and various immortalized keratinocyte cell lines differ from one other in their catalase activity. Moreover, deficient catalase activity appears to be related to the intensity of tumor phenotype expression. Since catalase activity in cell lines transformed in vitro is not as weak as activity observed in cell lines isolated from tumors, catalase deficiency may follow the successive steps of tumor progression.
Enhancement of azoxymethane‐induced colon carcinogenesis in spontaneously hypertensive rats
Authors: Tatsuta Masaharu , Iishi Hiroyasu , Baba Miyako , Taniguchi Haruo
Published: February 2007

The incidence, number, location, and histological types of colon tumors induced by azoxymethane (AOM) and the tissue norepinephrine concentration of the colon wall were investigated in spontaneously hypertensive (SH) rats and in control normotensive Wistar Kyoto (WKY) rats. All rats received 10 weekly s.c. injections of AOM. At week 30, the incidence of colon tumors was significantly higher in SH than in WKY rats. Colon tumors were chiefly located in the proximal colon in WKY but were found with significant frequency in the distal colon in SH rats. The colon tumors induced were mainly adenocarcinomas, but no significant difference in histological type of adenocarcinoma was found between the 2 strains of rat. At weeks 8 and 30, the norepinephrine concentration and labelling index of the distal colon, but not of the proximal colon, were significantly higher in SH than in WKY rats. These findings indicate that increased sympathetic nervous system activity enhances the development of colon tumors.
The use of a genotypic marker to demonstrate clonal dominance during the growth and metastasis of a human breast carcinoma in nude mice
Authors: Price Janet E. , Bell Carl , Frost Philip
Published: February 2007

When a mixture of 11 clones of a human breast carcinoma (MDA‐MB‐435)—each clone transfected with pSV2neo and identified as having a unique insertion site of the gene—was injected into nude mice, the resulting tumors were found to contain only one clone (Neo 24). This clone, identified by the unique restriction fragments on Southern blot analyses, was also found in metastases recovered from the lungs and lymph nodes of the animals. The individual clones showed no differences in in vitro growth, while in vivo the Neo 24 cells produced the largest tumors. Thus, one explanation for the observed clonal dominance in this study could be the more rapid growth in vivo of the Neo 24 cells. This study illustrates how an introduced selectable gene marker can be used in lineage studies of human tumor cell populations.
Cytokinetic investigation of lung tumors using the anti‐bromodeoxyuridine (BUDR) monoclonal antibody method: Comparison with dna flow cytometric data
Authors: Teodori Laura , Trinca Maria Luisa , Goehde Wolfgang , Hemmer Jorg , Salvati Franco , Storniello Giuseppe , Mauro Francesco
Published: February 2007

In order to investigate the cytokinetics of malignant tumors and non‐malignant lesions of the lung, tissue samples from 57 patients affected by non‐small‐cell carcinoma (NSCLC), small‐cell carcinoma (SCLC), and benign and inflammatory lesions have been analyzed using the BUdR monoclonal antibody (MAb) method. This method is based on the preparation, at the time of surgery, of viable monocellular suspensions (using collagenase and DNase treatment) and the concomitant administration of BudR. The percentage of BudR‐labelled cells was monitored by fluorescent microscopy using an FITC‐labelled second antibody. In NSCLC, each histological group showed a wide range of labelling index (LI) values. On the contrary, SCLC exhibited a more homogeneous kinetic behaviour as evidenced by a narrowly distributed, higher LI. Tumors shown to be diploid by flow cytometry did not show a lower LI than aneuploid tumors. Furthermore, differences were constantly observed between the S‐phase percent calculated using BUdR and that calculated using the DNA flow cytometric (FC) histogram, the latter always showing higher S‐phase values. In an attempt to study the intratumor proliferative heterogeneity, multiple‐site sampling was performed. Proliferative heterogeneity seemed to be higher inter‐tumor than intra‐tumor. Finally, a positive correlation (p < 0.05) was found between LI and the actual doubling time (DT) of the primary tumor mass, evaluated using sequential radiographs. In conclusion, the present BUdR method can be considered a useful source of relevant information on in vivo cell growth, in parallel to other clinical (DT) and biological (DNA content) approaches.
Purification and characterization of a peanut‐agglutinin‐binding pancreatic‐cancer‐related serum mucus glycoprotein
Authors: Ching C. K. , Rhodes Jonathan M.
Published: February 2007

A high‐molecular‐weight (approximately 3.5 × 103 kDa) peanut agglutinin (PNA)‐binding glycoprotein was previously identified as a tumour marker in pancreatic cancer sera. In the present study the density of this glycoprotein has been estimated and further analysis performed using sequential lectin blotting combined with serial mild acid hydrolysis followed by repeated Smith degradation. This has allowed partial in‐situ characterization of the carbohydrate side‐chains. The PNA‐binding glycoprotein variably expresses the blood group H and sialylated Lewisa antigens. H and sialyl Lea expression disappeared after mild acid hydrolysis and T (PNA acceptor) disappeared after the first Smith degradation step. T (βgal(1‐3)αgalNAc) expression reappeared after a second Smith degradation, suggesting that the backbone regions of the mucin side‐chains with this core sequence are built up by the further addition of at least 2 monosaccharides. A model has been constructed showing the minimum variations in side chain structure that would explain the results of the serial degradation and lectin blotting. Purification and caesium chloride density gradient centrifugation show that the infact PNA‐binding glycoprotein has a density of >1.48 g/ml, characteristic of a mucin. The development of assays using a panel of monoclonal antibodies (MAbs) or lectins directed against the different carbohydrate epitopes expressed on this mucin may provide better diagnostic accuracy for pancreatic cancer than current marker assays which rely on detection of a single epitope.
Inhibitory effect of quercetin on the synthesis of a possibly cell‐cycle‐related 17‐kDa protein, in human colon cancer cells
Authors: Hosokawa Nobuko , Hosokawa Yohei , Sakai Toshiyuki , Yoshida Mitsunori , Marui Nobuyuki , Nishino Hoyoku , Kawai Keiichi , Aoike Akira
Published: February 2007

Quercetin inhibits growth of COLO320 DM cells, derived from a human colon cancer. The inhibitory effect is partially reversible when quercetin is removed from the culture medium. Flow cytometric analysis has revealed that quercetin causes perturbation of the cell cycle, inducing a frozen cell‐cycle pattern and a block at the G1/S boundary. The synthesis of a 17‐kDa protein was specifically inhibited by the addition of quercetin, and recovered when the cells at the G1/S boundary progressed into S‐phase after the removal of quercetin from the culture medium. Furthermore, using synchronized cells obtained by centrifugal elutriation, we have shown that the rate of synthesis of a 17‐kDa protein was low in G1, and high in S‐phase of the cell cycle. Thus, this protein appears to be cell‐cycle‐related.
Differentiation capacity of human non‐small‐cell lung cancer cell lines after exposure to phorbol ester
Authors: Salge Ursula , Kilian Peter , Neumann Kurt , Elsässer Hans‐Peter , Havemann Klaus , Heidtmann Hans‐Heinrich
Published: February 2007

Three cell lines of squamous‐cell carcinoma and 3 of large‐cell carcinoma origin were investigated for the expression of differentiation markers and functional parameters (proliferation, morphology, cornified envelope formation, involucrin staining, transglutaminase activity, adhesiveness and migration) under normal cell culture conditions and after treatment with the tumor promoter phorbol‐12‐myristate‐13‐acetate (PMA). Although all original tumors had been described as poorly differentiated by histological grading, we found significant heterogeneity in the expression of differentiation markers in cell culture. A systematic grading of the cell lines became possible only after PMA stimulation. PMA generally increased expression of differentiation markers in cell lines of comparably low grades of differentiation, as indicated by dose‐dependent inhibition of proliferation and cloning efficiency, induction of squamous markers, and decreased adhesiveness and cell motility. In contrast, cell lines of apparently higher differentiation by these criteria showed little response to PMA. The results presented show that the assessment of differentiation capacity by comparison of differentiation markers under normal cell culture and PMA‐stimulated conditions in established NSCLC cell lines allows for a refined cell culture grading, which might advance the classification and characterization of such cell lines which, otherwise, appear to be very heterogeneous. It may also help to correlate cellular functions with various states of differentiation in vitro.
Differentiation and the tumorigenic and metastatic phenotype of murine melanoma cells
Authors: Kameyama Koichiro , Vieira Wilfred D. , Tsukamoto Katsuhiko , Law Lloyd W. , Hearing Vincent J.
Published: February 2007

Using B16 F10 murine melanoma cells and sublines generated from the JB/MS melanoma which exhibit various degrees of melanogenesis, the relationships among differentiation, tumorigenicity, and metastatic potential were examined. The effect of melanocyte‐stimulating hormone (MSH), which specifically stimulates differentiation of melanocytes, was also studied. All melanoma lines tested were capable of growing as experimental pulmonary metastases but, surprisingly, the undifferentiated and amelanotic JB/MS‐w cells failed to grow as primary subcutaneous tumors. JB/MS‐w cells, which had few surface MSH receptors, did not respond to MSH with an increase in melanin production, unlike the other cell lines. Although in vitro treatment with MSH did not change the rates of growth of primary tumors by these cell lines, such treatment decreased the number of pulmonary metastases from B16 F10, JB/MS cells, JB/MS‐b1 cells and JB/MS‐w cells. Conversely, MSH treatment significantly increased the rates of pulmonary metastases from JB/MS‐p cells. The expression of surface melanoma antigens, urokinase‐type plasminogen activity and susceptibility to natural killer cells were examined. MSH did not significantly alter surface melanoma antigen expression, but increased the natural killer cell susceptibility of B16 F10, JB/MS and JB/MS‐b1 cells, cells which possess abundant surface MSH receptors. There was an inverse correlation between differentiation (pigmentation) and proliferation in vitro, and the more pigmented melanoma cells (B16 F10, JB/MS and JB/MS‐b1) expressed relatively lower levels of class‐1 MHC, relatively higher levels of class‐11 MHC and the highest metastatic capacity. These results demonstrate that MSH possesses the capacity to regulate not only melanogenesis, but also other factors critical to the metastatic growth of the cells.
Inhibition of N‐methyl‐N′'‐nitro‐n‐nitrosoguanidine‐induced methotrexate and adriamycin resistance in CHO cells by adeno‐associated virus type 2
Authors: Yalkinoglu A. Özkan , Schlehofer Jö Rg R. , Hausen Harald Zur
Published: February 2007

We studied the effects of helper‐dependent parvovirus AAV [adeno‐associated virus] type 2 on carcinogen‐inducible resistance to methotrexate (MTX) and adriamycin (ADR) in Chinese hamster ovary cells. Both types of drug resistance were monitored by determination of the number of drug‐resistant colonies normalized for the respective value of plating efficiency under non‐selective conditions. Treatment of cells with N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG) drastically enhanced the frequency of resistance to MTX and ADR. By contrast, infection of cells with AAV‐2 prior to treatment with MNNG markedly inhibited carcinogen‐induced drug resistance. Infection by AAV alone did not exert any effect. Analysis of the dihydrofolate reductase (dhfr) gene copy numbers of individual MTX‐resistant clones derived from MNNG‐treated and non‐treated cultures revealed similar frequencies (60–18%) and amplitudes of dhfr gene amplification (2‐ to 8‐fold) irrespective of prior AAV treatment. Hence, carcinogen‐induced enhancement of MTX‐resistance could reflect an increase in the frequency of dhfr gene amplification among the survivors of MNNG treatment. On the other hand, inhibition of carcinogen‐inducible drug resistance by AAV suggests an interference of the virus with cellular responses to genotoxic stress, thus leading to enhanced cell killing under altered growth conditions. Possible mechanisms responsible for the inhibitory effect of AAV and its relevance in relation to tumor chemotherapy are discussed.
Presence of hpv 16 sequences in laryngeal carcinomas
Authors: Pérez‐ayala M. , Ruiz‐Cabello F. , Esteban F. , Concha A. , Redondo M. , Oliva M. R. , Cabrera T. , Garrido F.
Published: February 2007

Human papillomavirus types HPV 16 and HPV II DNA sequences were analyzed in normal and neoplastic tissues of the larynx, using the technique of polymerase chain reaction (PCR). An amplified region of E6 ORF was hybridized with 3′ end‐labelled oligonucleotide probe. Twenty six out of 48 (54%) squamous‐cell carcinomas, and 3 out of 3 verrucous‐cell carcinomas hybridized with HPV 16 DNA sequences, whereas we did not detect HPV II sequences. HPV 16 DNA sequences were also found in normal, autologous mucosa and lymphnode metastases, although these were absent in other tissues analyzed. HPV‐16‐positive tumors were most frequently poorly differentiated squamous‐cell carcinomas.
Human meningiomas co‐express platelet‐derived growth factor (pdgf) and pdgf‐receptor genes and their protein products
Authors: Maxwell Marius , Galanopoulos Theofanis , Tessa Hedley‐Whyte E. , McL. Black Peter , Antoniades Harry N.
Published: February 2007

The present studies investigated the expression of the platelet‐derived growth factor (PDGF) and PDGF‐receptor genes in human meningiomas. Northern blot analysis demon strated that all meningiomas examined expressed both the c‐sis/PDGF‐2 proto‐oncogene and the PDGF‐receptor gene. In situ hybridization localized the c‐sis mRNA and the PDGF receptor mRNA in the tumor cells of the meningioma tissues. Control pachymeninges derived from adult individuals, with out meningiomas, expressed only PDGF‐receptor mRNA but not the c‐sis mRNA. Immunocytochemistry studies detected both the c‐sis and the PDGF‐receptor protein products in me ningioma tissues but only the PDGF‐receptor protein prod ucts in control pachymeninges. These findings indicate the presence of an autocrine mechanism in human meningiomas based on the co‐expression of the c‐sis/PDGF‐2 proto‐onco gene and PDGF‐receptor gene and their protein products. This co‐expression of a potent mitogen and its receptor may contribute to the growth and maintenance of human menin giomas.
Circulating antibodies against c‐MYC oncogene product in sera of colorectal cancer patients
Authors: Ben‐Mahrez Kamel , Sorokine Irène , Thierry Dominique , Kawasumi Toshiyuki , Ishii Sunsuke , Salmon Remy , Kohiyama Masamichi
Published: February 2007

We developed a Western blot assay using purified human c‐myc protein expressed in E. coli in order to look for circulating anti‐c‐myc antibodies in human sera. The presence of IgG antibodies against c‐myc was observed in 25 out of 44 sera from patients with colorectal cancer diagnosed and treated at the Hǒpital Curie in Paris, compared to the sera of 46 normal donors of which only 8 samples were positive (p = 0.001).