bluuebunny/crossref_metadata_2025 huggingface dataset:
Epstein‐Barr viral serology in nasopharyngeal carcinoma patients in the USSR and Cuba, and its value for differential diagnosis of the disease
Authors: Gurtsevitch V. , Ruiz R. , Stepina V. , Plachov I. , le Riverend E. , Glazkova T. , Lavoué M.‐F. , Paches A. , Aliev B. , Mazurenko N.
Published: February 2007

Serological responses to Epstein‐Barr virus (EBV)‐associated antigens were studied in nasopharyngeal carcinoma (NPC) patients in 2 countries non‐endemic for the disease: the USSR (77 cases) and Cuba (55 cases). Two age‐ and sex‐matched control groups were available, one consisting of patients with other head‐and‐neck tumours (OHNT) (171 from the USSR and 56 from Cuba), and the other of normal individuals (blood donors) (83 from the USSR and 80 from Cuba). Unlike the control groups, NPC patients from both countries had high levels of IgG and IgA antibodies, similar to those seen in patients from endemic areas. The only difference between NPC patients in the USSR and those in Cuba was lower (2–2.5 fold) anti‐VCA IgG and IgA antibody titres. Using one‐factor and multi‐factor statistical methods the diagnostic value of different titres of EBV‐specific IgG and IgA antibodies and their combinations for NPC patients (in the USSR) was evaluated. It was found that with simple mathematical analysis of EBV‐specific antibody titres a differential diagnosis of NPC could be made to a significance level of 90%. The data obtained demonstrated the importance and reliability of EBV serology in the diagnosis of NPC in areas of low incidence of the disease.
HTLV‐I carriers among migrants from an ATL‐endemic area to ATL non‐endemic metropolitan areas in Japan
Authors: Tajima Kazuo , Tominaga Suketami , Suchi Taizan , Fukui Hisao , Komoda Haruko , Hinuma Yorio
Published: February 2007

The prevalence of antibodies against HTLV‐I among Kyushu natives aged 16 to 39 years who moved from Nagasaki and Kagoshima prefectures to Aichi prefecture (a non‐endemic area for ATL) was compared by their cities or counties of birth. The positive rate of anti‐HTLV‐I antibody was 2.4% (II/400) among Nagasaki natives, 6.4% (20/312) among Kagoshima natives and 4.0% (31/772) for both combined. There was a slight difference in the positive rate of anti‐HTLV‐I antibody between Kyushu natives from cities (3.3%) and from counties (4.5%). In county areas, the prevalence of anti‐HTLV‐I antibodies among migrants from areas of relatively higher mortality for malignant lymphomas (7.5%) was significantly higher (p<0.01) than among persons from lower mortality areas (1.9%). Most “positive” persons had moved from Kyushu to Aichi prefecture between the ages of 15 and 18 years. The results of the present study suggest that: (1) there is a considerable number of HTLV‐I carriers among Kyushu natives who have settled in ATL non‐endemic areas, especially among those born in regions of Kyushu district which have a high mortality rate for malignant lymphomas; and (2) that Kyushu natives who had settled in metropolitan areas might have been exposed to HTLV‐I during childhood in their birthplace.
Beta‐carotene levels in exfoliated mucosa cells of population groups at low and elevated risk for oral cancer
Authors: Stich Hans F. , Hornby A. Paul , Dunn Bruce P.
Published: February 2007

Beta‐carotene was estimated in exfoliated oral mucosa cells in groups of individuals at various risks for oral cancer. Approximately 4 × 106 exfoliated cells were collected from each subject by brushing the oral mucosa. Cell pellets were hydrolyzed with pronase and then with KOH/methanol. Beta‐carotene was extracted with hexane, separated by reverse‐phase HPLC, and detected at 450 nm. Mean beta‐carotene levels in exfoliated cells were 0.08 ng/106 cells for 56 heavy consumers of alcoholic beverages (150 g or more per week), 1.36 ng/106 cells for 28 Seventh Day Adventists (all abstainers from alcohol, tobacco and meat consumption), 1.39 ng/106 cells for 55 lacto‐vegetarians of the International Society for Krishna Consciousness (ISKC) (abstainers from alcohol and tobacco), and 1.08 ng/106 cells for 61 representatives of a “Western” lifestyle pattern (64% consumed the equivalent of at least one bottle of wine or 7 bottles of beer per week, and all were non‐smokers). If the heavy alcohol consumers (males) are matched to non‐drinking males of comparable age, the mean beta‐carotene values are 0.08 ng versus 1.24 ng/106 cells. The possible involvement of the low levels of beta‐carotene in the mucosa of heavy alcohol drinkers in increased sensitivity towards the carcinogenic and genotoxic activity of cigarette smoking plus alcohol ingestion is discussed.
Multistep process of neoplastic transformation of normal human fibroblasts by 60CO gamma rays and harvey sarcoma viruses
Authors: Namba Masayoshi , Nishitani Koji , Fukushima Fujiko , Kimoto Tetsuo , Nose Kiyoshi
Published: February 2007

As reported previously (Namba et al., 1985), normal human fibroblasts were transformed by 60Co gamma‐ray irradiation into immortal cells with abnormal karyotypes. These transformed cells (KMST‐6), however, showed a low cloning efficiency in soft agar and no transplantability. However, upon treatment with Harvey murine sarcoma virus (Ha‐MSV), the cells acquired elevated clonability in soft agar and transplantability in nude mice. Ha‐MSV alone, however, did not convert normal human fibroblasts into either immortal or tumorigenic cells. The Ha‐MSV‐transformed KMST‐6 cells showed an enhanced expression of the ras oncogene, but normal and 60Co gamma‐ray‐transformed cells did not. Our current data suggest that gamma rays worked against normal human cells as an initiator, giving rise to chromosome aberrations and immortality, and that Ha‐MSV, probably through its ras oncogene, played a role in the progression of the malignant cell population to a more malignant one showing enhanced colony formation in soft agar and tumorigenicity in nude mice.
Comparative study on pyruvate kinase activity‐reducing action of various promoters of hepatocarcinogenesis
Authors: Yanagi S. , Sakamoto M. , Nakano T.
Published: February 2007

Chemicals such as PB, DDT, EED, sodium deoxycholate, thiobenzamide, orotic acid and SorFAE which enhance the formation of liver tumors or HN, caused a marked decrease in PK activity in Wistar rat liver that persisted for at least 4 weeks, though the decrease caused by EED was not so marked as that caused by other hepatic promoters. Non‐promoting agents such as DH, and some chemicals, such as DEXA, testosterone and AB, which enhance the formation of GGT‐positive foci in rat livers, but do not enhance the formation of tumors or HN, caused decreases in PK activity in some cases. Any such decreases, however, were only transient and normal levels were restored within 4 weeks. The results suggest that the continuous decrease in PK activity may be a useful marker in screening tests for the promoters of hepatocar‐cinogenesis.
Synergistic antileukemic effect of two polyamine synthesis inhibitors. Host survival and cell‐cycle kinetic analysis
Authors: Ask Anders , Persson Lo , Oredsson Stina M. , Heby Olle
Published: February 2007

α‐Difluoromethylornithine (DFMO), an enzyme‐activated irreversible inhibitor of ornithine decarboxyl‐ase, was used alone and in combination with multiple doses of methylglyoxal‐bis(guanylhydrazone) (MGBG) to treat mice with systemic L1210 leukemia. Used as a single agent (administered p.o. as a 3% solution in tap water), DFMO exerted a weak therapeutic effect against this tumor. The therapeutic effect of MGBG (administered i.p. at 50 mg/kg/day) was only slightly better. However, 1–3 days of pretreatment with DFMO strongly potentiated the effect of MGBG treatment. Thus, mice treated with the combination exhibited an increase in life span of up to 138%. The prolonged survival of leukemic mice treated with a combination of DFMO and MGBG was associated with inhibition of polyamine synthesis and a marked decrease in the spermidine and spermine content of the tumor cells as compared to untreated controls. As a consequence, there was a continuous decrease in the S‐ and G2‐phase fractions with a concomitant increase in G1. Used singly, DFMO and MGBG had no significant effect on the cell‐cycle distribution. The effects of the combination of DFMO and MGBG on the cell‐cycle distribution are consistent with the contention that polyamine deficiency primarily interferes with initiation of DNA synthesis. However, the possibility that selective S‐phase kill partly contributes to this change in cell‐cycle distribution cannot be excluded.
Adenosine deaminase complexing protein (ADCP) immunoreactivity in colorectal adenocarcinoma
Authors: Kate Joop Ten , van de Ingh Harry F. G. M. , Khan P. Meera , Bosman Fré T.
Published: February 2007

Immunoreactive adenosine deaminase complexing protein (ADCP) was studied in 91 human colorectal adenocarcinomas. The expression of ADCP was correlated with that of secretory component (SC) and carcinoembryonic antigen (CEA), with the histological grade and the Dukes' stage of the carcinomas. The histological grade was scored semi‐quantitatively according to 5 structural and 4 cytological variables. ADCP expression was observed in 3 different staining patterns, namely: (1) diffuse cytoplasmic (77% of the carcinomas); (2) granular cytoplasmic (13%); and (3) membrane‐associated (66%). These patterns were observed alone or in combination. Eleven percent of the carcinomas exhibited no ADCP immunoreactivity. Linear regression analysis showed that the expression of ADCP correlates with that of SC and CEA. However, no significant correlation emerged between the histological parameters or the Dukes' stage and any of the immunohistological parameters. Comparison of the histological characteristics of carcinomas exhibiting little or no ADCP immunoreactivity with those showing extensive immunoreactivity, showed that membranous ADCP immunoreactivity occurs more frequently in well‐differentiated carcinomas. Structural parameters showed a better correlation with membranous ADCP expression than the cytological variables. It is concluded that membranous expression of ADCP and CEA are indicators of a high level of differentiation as reflected primarily in the structural characteristics of the tumor.
Use of monoclonal antibodies to human breast‐tumor‐associated antigens in fine‐needle aspirate cytology
Authors: Nuti M. , Mottolese M. , Viora M. , Donnorso R. Perrone , Schlom J. , Natali P. G.
Published: February 2007

Fine‐needle aspiration cytology (FNAC) is currently used in evaluating the nature of breast nodules. In the present study we have examined whether monoclonal antibodies (MAbs) to breast‐tumor‐associated antigens (BTAA) can be employed in FNAC for the diagnosis of breast cancer. For this purpose we have used 2 murine MAbs recognizing 2 distinct BTAA expressed by breast tumors, irrespective of their histotype, in an indirect avidin‐biotin immunohistochemical technique on aspirate smears. The results of this study show that, while benign lesions are consistently negative, tumor cells containing aspirates are reactive with at least one MAb in 95% of the cases. Thus, selected MAbs to BTAA may be a powerful diagnostic tool in conjunction with conventional cytology, and because of the objective interpretation of the immunohistochemical findings, FNAC of the breast can eventually be extended outside specialized institutions.
Molecular cloning of two new HPV types (HPV 37 and HPV 38) from a keratoacanthoma and a malignant melanoma
Authors: Scheurlen Wolfram , Gissmann Lutz , Gross Gerd , Hausen Harald Zur
Published: February 2007

Several benign and malignant skin tumors were analyzed for the presence of human papillomavirus (HPV) DNA. By hybridization with different HPV DNA probes under non‐stringent conditions (Tm −40° C), two tumors were found to contain HPV‐specific DNA sequences in high copy numbers: (1) a keratoacanthoma from a patient who also suffered from a basalioma; (2) a superficial spreading malignant melanoma of an immunosuppressed patient. For further analysis of these DNA sequences genomic libraries from both tumour DNAs were constructed and, out of these, 4 different HPV DNA types have been cloned. By cross‐hybridization experiments and restriction map analysis HPV 9 DNA was identified in the keratoacanthoma whereas HPV 17a DNA could be cloned from the malignant melanoma. From each tumor one additional HPV‐type not identical to other known HPV‐types was cloned. These isolates are closely related to HPV 9, 15, 17, 22 and 23. A physical map of both HPV DNAs was constructed. Size (7.8 kbp), co‐linear alignment to HPV 16, cross‐hybridization with other HPV‐types under conditions of low stringency and monomic episomal state of the HPV molecules indicate that these two DNA probes represent new HPV types that have been tentatively designated as HPV 37 (keratoacanthoma) and HPV 38 (malignant melanoma). None of these two HPV types could be found in any other of 231 tumor DNAs originating from different tissues.
Clonal evolution of T‐cell chronic lymphocytic leukaemia in a patient with ataxia telangiectasia
Authors: Taylor A. M. R. , Butterworth S. V.
Published: February 2007

Ataxia telangiectasia (A‐T) is an autosomal recessive disorder in which patients show an unusual predisposition to malignant disease, including T‐cell chronic lymphocytic leukaemia. We report here the steady growth over 5 years of a complex, cytogenetically abnormal clone of T lymphocytes in an A‐T patient who was subsequently found to have an OKT3/OKT8 chronic lymphocytic leukaemia. The tumour cells at diagnosis had clearly evolved from a pre‐existing, cytogenetically abnormal T‐cell clone which contained an inv(14) chromosomal inversion alone.
Recurrent chromosome abnormalities in adult T‐cell lymphomas of peripheral T‐cell origin
Authors: Fujita Kazuyuki , Fukuhara Shirou , Nasu Kaori , Yamabe Hirohiko , Tomono Naomi , Inamoto Yasuhiko , Shimazaki Chihiro , Ohno Hitoshi , Doi Shoichi , Kamksaki Hiroshi , Ueshima Yoshimi , Uchino Haruto
Published: February 2007

Cytogenetic studies were performed on 11 Japanese patients with adult T‐cell lymphoma of peripheral T‐cell origin. All patients had a histologic diagnosis of diffuse lymphoma, and were treated with intensive combination chemotherapy; their median survival was 6 months. Lymphomas were categorized on the basis of the classification proposed by the Lymphoma Study Group of Japan: 5 patients had the features of pleomorphic lymphoma; 3, mixed lymphoma; 2, large‐cell lymphoma; and 1, medium‐sized‐cell lymphoma. The modal chromosome number of abnormal cells was near‐diploid in 7, and hypotetraploid in 4 including 3 patients with pleomorphic lymphoma. Abnormalities of the clonal chromosomes were observed in all 11 patients. A translocation of the short arm of 19 at band 19p13 was found in 2 patients with pleomorphic lymphoma and in one patient each with mixed lymphoma and medium‐sized‐cell lymphoma. A transloction of the short arm of 14, with a break at band 14p12, occurred in 4 patients with pleomorphic lymphoma. In one patient each with mixed lymphoma and large‐cell lymphoma, an extra chromosome 3 was found. The numerical change was unique because their lymphomas were further categorized as “angioimmunoblastic lymphadenopathy with dysproteinemia” and “large‐cell immunoblastic lymphoma”, respectively. Our findings suggest that characteristic chromosome abnormalities occur in adult T‐cell lymphoma, and dividing cells in the tetraploid range tend to be precominant in pleomorphic lymphoma.
Procoagulant activity of human alveolar macrophages: Different expression in patients with lung cancer
Authors: Semeraro Nicola , De Lucia Onofrio , Lattanzio Angela , Montemurro Pasqualina , Giordano Domenico , Loizzi Michele , Carpagnano Francesco
Published: February 2007

Mononuclear phagocytes, an integral part of the lymphoreticular infiltrate of many malignant tissues, might contribute to tumor‐associated fibrin deposition through the production of procoagulant activity (PCA). We have studied the PCA of human alveolar macrophages in 28 patients with primary lung cancer and in 9 control subjects. Alveolar macrophages (> 97% esterase positive) were isolated from bronchoalveolar lavage fluids by adherence onto plastic. PCA was evaluated by a one‐stage clotting assay immediately after isolation (basal PCA) and after incubation ( hr at 37°C) in the absence and in the presence of endotoxin. Cells from control subjects had low basal PCA (3.9 ± 1.0 units/5 × 104 cells) but, upon exposure to endotoxin, they displayed a 5‐ to 16‐fold increase in PCA. In patients, different patterns of PCA were observed. In the 8 patients in whom lavage had been carried out on the contralateral side to the neoplasm, alveolar macrophages behaved essentially like those from controls. In contrast, in the 20 patients in whom macrophage populations close to the site of the tumor were examined, PCA was abnormal in many respects. ± 12 of these, alveolar macrophages had basal PCA comparable to or somewhat lower than control cells, but exhibited a poor procoagulant response when incubated in vitro in the presence of endotoxin. Alveolar macrophages from the remaining 8 patients expressed far higher levels of basal PCA than control cells (25.1 ± 5.9 units as compared to 3.9 ± 1.0 units/5 × 104 cells). These cells retained their ability to respond to endotoxin in vitro with a 3‐fold increase in PCA. In all instances, alveolar macrophage PCA had the characteristics of tissue factor. These data suggest that the presence of primary lung cancer may moduate the expression of PCA in alveolar macrophages close to the tumor site. PCA might be useful to better characterize the functional state of macrophages near the tumor.
Morphology of bronchogenic carcinoma in workers formerly exposed to crocidolite at wittenoom gorge in Western Australia
Authors: Baker J. E. , Reutens D. C. , Graham D. F. , Sterrett G. F. , Musk A. W. , Hobbs M. S. T. , Armstrong B. K. , de Klerk N. H.
Published: February 2007

Cytology and histology material from 46 bronchogenic carcinomas occurring in ex‐workers from the Wittenoom crocidolite mine and mill in Western Australia and a matched random sample of 234 other bronchogenic carcinomas occurring in Western Australia over the same period were reviewed by a single histopathologist without knowledge of asbestos exposure status. Squamous‐cell carcinomas formed 45.7% of the cancers in the asbestos‐exposed group but only 32.5% of the cancers in the comparison group. This difference could not be explained by differences in smoking history between the two groups of lung cancer patients or in the type of histopathological material available for review. The excess of squamous‐cell cancers was observed in subjects both with and without parenchymal asbestosis.
Detection of DNA cross‐links in tumor cells with the ethidium bromide fluorescence assay
Authors: de Jong S. , Zijlstra J. G. , Timmer‐Bosscha H. , Mulder N. H. , de Vries E. G. E.
Published: February 2007

Until now the fluorescence assay with ethidium bromide has only been used on pure DNA. This assay depends on the difference in fluorescence between single‐ and double‐stranded DNA (dsDNA). Cross‐links in DNA are measured by the return of fluorescence of dsDNA after heat denaturation at ph 12. Under these conditions denatured DNA gives very low fluorescence. In the present study this assay was applied to tumor cells. The mouse Ehrlich ascites tumor cell line (EAT) and a human small‐cell carcinoma line (GLC4) were incubated for 4 hr at 37° C, with the cross‐linking agent cis‐diamino‐dichloro platinum (cDDP). The samples of whole cells were thereafter resuspended in potassium phosphate buffer with 10 mm EDTA, 4m NaCI, 0.1% Sarkosyl ph 7.2, for 16 hr at 37° C. Measurements were performed with a spectrofluorometer with excitation wavelength 525 nm, emission wavelength 580 nm. There was a linear relationship for cDDP concentrations of 0–150 μm and the extent of DNA cross‐links in EAT (r = 0.958). In GLC4 there was a linear relationship at low cDDP concentrations of 0–50 μm (r = 0.968) while between 50 and 150 μm a plateau was reached. RNase added to the lysate of whole cells had no influence on the extent of cross‐links. This assay was compared with the alkaline elution assay, and results were identical.
Altered glycosylation of membrane glycoproteins in human uroepithelial cell lines
Authors: Debray Henri , Qin Zhu , Delannoy Philippe , Montreuil Jean , Duś Danuta , Radzikowski Czeslaw , Christensen Britta , Kieler Jørgen
Published: February 2007

Total cellular glycopeptides of 7 human uroepithelial cell lines that differ in the grade of transformation (TGr) were analysed by gel filtration and affinity chromatography on immobilized lectins. The 4 cell lines that are tumorigenic in nude mice and invasive in vitro (TGr III) possess more highly branched, tri‐ and tetraantennary N‐acetyllactosaminic glycans, with less biantennary glycans than the 2 non‐tumorigenic, non‐invasive (TGr II) cell lines examined. The only exception to this general pattern is the third cell line, which is classified as TGr II. The cellular glycopeptide distribution pattern in this cell line is similar to that of the TGr III cells. The possible relationship between altered glycosylation of membrane glycoproteins and the expression of a malignant phenotype is discussed.
Incidence of bovine leukemia virus‐specific antibodies in west african cattle
Authors: Walrand Francoise , Fumoux Francis , Roelants Georges , Parodi André‐Laurent , Levy Daniel
Published: February 2007

A sero‐epidemiological survey of bovine leukemia virus (BLV) infection in indigenous West African cattle was undertaken using a radioimmunoassay and enzyme‐linked immunosorbent assay. A high incidence of anti‐BLV antibodies was found in the breeds tested and their crosses, whatever the test used. More extensive studies are needed to establish the prevalence of BLV infection in other parts of Africa; these may provide additional data on the similarities found between human and bovine leukemia viruses.
Protein phosphorylation at tyrosine residues IN v‐abl transformed mouse lymphocytes and fibroblasts
Authors: Saggioro D. , Ferracini R. , Di Renzo M. F. , Naldini L. , Chieco‐Bianchi L. , Comoglio P. M.
Published: February 2007

Phosphotyrosine antibodies were employed to immunodecorate and immunoprecipitate proteins phosphorylated at tyrosine residues in cells transformed by Abelson murine leukemia virus (A‐MuLV). In pre‐B and pre‐T lymphoma cells transformed by A‐MuLV, the major phosphotyrosine‐containing protein has an MW of 160 kDa and shares immunologically detectable sequences with the v‐abl oncogene product. Moreover, two different proteins of approximately 100 and 68 kDa, heavily phosphorylated at tyrosine, were identified. Lack of immunological cross‐reactivity with viral products and phosphopeptide mapping showed that the 100 and 68 kDa proteins are coded by cellular genes. Phosphoproteins were undetectable in control resting lymphocytes. The 68 and the 100 kDa proteins were phosphorylated to different extents in proliferating lymphocytes, either stimulated by the growth factor IL‐2, or transformed by M‐MuLV (lacking the oncogene coded kinase). In fibroblasts transformed by A‐MuLV, phosphotyrosine antibodies identified 2 proteins of 120 and 70 kDa. By immunological cross‐reaction and by phosphopeptide mapping, the first was identified as a 120 kDa form of the v‐abl coded kinase. The 70 kDa protein is coded by a cellular gene, is not structurally related to the 120 kDa v‐abl kinase, and is different from any phosphotyrosine‐containing protein detected in A‐MuLV‐transformed lymphocytes. These data show that, upon v‐ablinduced transformation, phosphorylation at tyrosine takes place also on proteins other than the 160 or 120‐kDa oncogene products. In lymphocytes and fibroblasts these proteins are different, suggesting that the cascade of events triggered by the v‐abl gene in different cell types involves tyrosine phosphorylation of different specific proteins.
Natural killer‐cell immunodeficiency in patients with chronic myelogenous leukemia. I. Analysis of the defect using the monoclonal antibodies HNK‐1 (LEU‐7) and B73.1
Authors: Fujimiya Yoshiaki , Bakke Anthony , Chang Weng Cheng , Linker‐Israeli Marianna , Udis Barry , Horwitz David , Pattengale Paul K.
Published: February 2007

Quantitative evaluation of natural killer (NK) cells using the HNK‐I (Leu‐7) and B73.1 monoclonal antibodies (MAbs) was correlated with NK activity in 13 patients with chronic myelogenous leukemia (CML) and compared to normal donor controls. A consistent observation was the presence of normal absolute numbers of B73.1 + lymphocytes as well as normal to increased absolute numbers of HNK‐I + lymphoid cells in the peripheral blood of chronic‐phase CML patients. Despite normal to increased numbers of B73.1 + and HNK‐I + lymphoid cells, these patients consistently demonstrated a significant impairment of lymphocyte‐mediated NK activity in their peripheral blood. Further experiments demonstrated that chronic‐phase CML patients, in contrast to normal controls, had significantly increased percentages of HNK‐I +, E+ and B73.1 +, E+ lymphoid cells and significantly decreased percentages of HNK‐I +, E− and B73.1, E− lymphoid cells, which resulted in significant reversals of the HNK‐I +, E+ to HNK‐I+, E− and B73.1+, E+ to B73.1 +, E− lymphoid cell ratios. (HNK‐I + [E+/E−] > B73.1+ E + [E+ /E−]). Furthermore, as compared to normals, both FACS‐sorted HNK‐I+ and B73.1 + lymphoid cells from the E+ fraction of CML patients were consistently defective in NK activity, and could not be substantially augmented with α‐interferon preparations. Although markedly defective in their ability to lyse K‐562, HNK‐I + lymphoid cells from the E+ fraction of CML patients were not defective in their ability to bind to the NK‐sensitive target, K‐562. In contrast, NK‐defective B73.1 + lymphoid cells were partially defective in their ability to bind to K‐562.
The copenhagen case‐control study of bladder cancer. II. Effect of coffee and other beverages
Authors: Jensen O. M. , Wahrendorf J. , Knudsen J. B. , Sørensen B. L.
Published: February 2007

During the years 1979–1981 a population‐based case‐control study of bladder cancer including papilloma was performed in greater Copenhagen. A total of 371 patients (280 males; 91 females), and a comparable age‐and sex‐stratified group of 771 controls (577 males; 194 females) remained for logistic regression analysis. Controls were selected at random from the general population of the study area. All persons were questioned about their drinking habits with respect to coffee, tea and other beverages, as well as their exposure to a number of known or suspected risk factors for bladder cancer. After adjustment for tobacco smoking, the relative risk of bladder cancer in relation to coffee drinking was not statistically significant among either men or women. A significant association was found between bladder cancer and tea drinking among men, but with no regular trend for increasing consumption. An association was found between risk of bladder cancer and both total daily liquid intake and non‐cola soft drinks. This population‐based case‐control study provides no evidence of an isolated influence of coffee drinking or caffeine intake on bladder cancer risk.
Detection of IgG and IgA antibodies to epstein‐barr virus membrane antigen in sera from patients with nasopharyngeal carcinoma and from normal individuals
Authors: Zhu X. X. , Zeng Y. , Wolf H.
Published: February 2007

IgG and IgA antibodies to Epstein‐Barr virus (EBV) membrane antigen (MA) were detected in sera from 96 NPC patients and normal individuals by the indirect immunofluorescence test. For MA/IgG antibody, 100% of NPC patients were positive with a GMT of 1:439.7 and 97.9% of normal individuals were positive with a GMT of 1:94.7. In contrast, for MA/IgA antibody, 58.3% of NPC patients were positive with a GMT of 1:7.3 and none of the normal individuals were positive. There was no difference in the detection of antibodies to EBV MA when other P3HR‐1 or B95‐8 cell lines, differing in their major membrane antigen, were used.
Measurement of a pancreatic cancer‐associated antigen (DU‐PAN‐2) detected by a monoclonal antibody in sera of patients with digestive cancers
Authors: Sawabu Norio , Toya Daishu , Takmori Yasuhiro , Hattori Nobu , Fukui Masanori
Published: February 2007

DU‐PAN‐2 is a high‐molecular‐weight glycoprotein defined by a murine monoclonal antibody (MAb) against a pancreatic ductal adenocarcinoma cell line. In order to evaluate the usefulness of this antigen as a tumor marker, we determined the serum level of the antigen by competitive inhibition radioimmunoassay in sera from 139 patients with various malignant tumors, chiefly digestive cancers, 98 patients with different benign diseases and 11 healthy subjects. Values in the healthy subjects were less than 100 U/ml. Levels above 100 U/ml were frequently observed in sera from benign diseases, but levels above 400 U/ml were found in only 6 of the patients with benign diseases. In contrast, levels exceeding 400 U/ml were detected in 72% of patients with pancreatic cancer, 44% of patients with hepatocellular cancer and 40% of patients with biliary tract cancer. The positivity was low in other cancers such as gastric cancer (19%) and colorectal cancer (7%). Serum levels of CEA and CA 19–9 were rlso determined in cancer patients. Among the pancreatic cancer patients studied, values above 400 U/ml were found in 5 of the 8 CEA‐negative patients (< 5 ng/ml) and 2 of the 3 CA 19–9 negative patients (< 37 U/ml). These results indicate that determination of the serum DU‐PAN‐2 can aid in serological diagnosis of cancer of the digestive tract, more particularly of the pancreas.
Selective suppression of metastasis but not tumorigenicity of a mouse lung carcinoma by cell hybridization
Authors: Layton M. G. , Franks L. M.
Published: February 2007

Somatic cell hybrids were produced by polyethylene glycol‐induced cell fusion between metastatic CMT167 (HGPRT−/OUAR) C57BL/Icrfat mouse lung carcinoma cells and 2 non‐metastatic cell lines: C3H/He mouse L‐M(TK−) cells of mesenchymal origin and EJ (OUAS) human bladder carcinoma cells. Fusion of 2 different CMT167 (HGPRT−) clones with L‐M(TK−) cells followed by selection in HMT medium gave rise to 14 intraspecific hybrids, which were shown to express H‐2 antigens specific for both the C57 and C3H mouse strains. Three interspecific hybrids arising from fusion of EJ(OUAS) and CMT167(HGPRT−/OUAR) cells were selected in HMT/ouabain medium and characterized by human isozyme analysis. All the hybrids produced large tumours after subcutaneous inoculation of 5 × 105 cells into adult athymic nu/nu mice. The intraspecific hybrid tumours were predominantly sarcomatous (mesenchymal) in structure but a few contained epithelial acini. Metastatic ability (as assessed by production of lung metastases) was completely suppressed in 13 of the 14 mouse/mouse hybrid cell clones. These results suggest that tumorigenicity, tumour structure and the ability to metastasize are expressed independently. The interspecific hybrids, which had not retained a full human chromosome complement, produced metastatic tumours that remained epithelial in structure.
A synergistic effect between anti‐idiotype antibodies and anti‐neoplastic drugs in the therapy of a murine B‐cell tumor
Authors: Hurwitz E. , Burowski D. , Kashi R. , Hollander N. , Haimovich J.
Published: February 2007

Antibodies directed against idiotypic determinants of the cell‐surface IgM of a B lymphoma, 38c, were effective in delaying development of the tumor and in some instances in preventing its growth. The efficacity of the anti‐idiotype antibodies was markedly increased when they were injected in combination with anti‐neoplastic drugs. Since chemotherapy, as such, is limited by the general toxicity of the drugs it was of advantage to apply them in low doses. The drug doses used were mostly ineffective by themselves, yet were active in combination with the antibody in a more than additive fashion. We performed studies designed to elucidate the mechanism of the synergy between the anti‐idiotype antibodies and the drugs. The data suggest that the activity of the antibody is partly indirect and is mediated through the host's effector cells. In the case of one drug, daunomycin, the activity is also, at least in part, mediated through peritoneal exudate cells (PEC). Daunomycin injected intraperitoneally activated PEC. Such activated PEC, when injected into recipient mice, could replace the drug in its synergy with the antibody. In conclusion, it was shown that it is possible to increase the effectiveness either of antibodies to tumor cells or of cytotoxic drugs by combination therapy.
Lectin binding glycoproteins in human melanoma cell lines with high or low tumorigenicity
Authors: Berthier‐Vergnes Odile , Réano Alain , Doré Jean‐François
Published: February 2007

Lectin binding glycoproteins of 5 human malignant melanoma cell lines (HMMCL), differing in their ability to grow subcutaneously in athymic nude mice, were compared by electrophoresis of total cellular proteins and subsequent incubation of SDS‐poly‐acrylamide gel with 125I‐labelled lectins. Despite the similarity between the protein profiles of the different HMMCL, Concanavalia ensiformis agglutinin (ConA), wheat‐germ agglutinin (WGA) and peanut agglutinin (PNA) revealed differences in their glycoprotein expression, in contrast with Ulex europaeus agglutinin I (UEA 1). A great diversity was observed in the electrophoretic mobilities and/or staining intensities of ConA and WGA binding glycoproteins of HMMCL. However, neither ConA‐reactive glycoproteins nor WGA‐reactive glycoproteins could be detected that were characteristic of HMMCL with high tumorigenicity (HT) or low tumorigenicity (LT). In contrast, the expression of two cell‐surface PNA binding glycoproteins appeared to be related to the tumorigenic phenotype of HMMCL. One of them, with an apparent molecular weight of 190 kDa, was only detected in the LT cell lines. The other, with an apparent molecular weight of 60 kDa, was detected in all HMMCL but became strongly labelled after neuraminidase treatment only in the HT cell lines. Thus, the expression of glycoproteins rich in terminal galactose residues may characterize human melanoma cells with different tumorigenic behavior.
Metabolic and morphologic changes in brown adipose tissue from non‐growing mice with an isogeneic sarcoma. Evaluation with respect to development of cachexia
Authors: Edström Staffan , Kindblom Lars‐Gunnar , Lindmark Lars , Lundholm Kent
Published: February 2007

Brown adipose tissue plays a thermoregulatory role influencing energy balance in experimental animals and possibly also in humans. In the present study we have reevaluated whether brown adipose tissue may contribute to the development of cancer cachexia in non‐growing mice bearing an isogeneic tumor. Interscapular brown adipose tissue mass decreased by 20% in freely‐fed sarcoma‐bearing mice housed at room temperature. Increased mitochondrial density and increased oxidation rate of acetate at low acetate concentrations were found in brown fat from sarcoma‐bearing mice, while the oxidation capacity was unchanged compared with that of freely‐fed controls. Metabolic and morphologic changes in brown fat from sarcoma‐bearing mice were similar to those found in weight‐paired controls, which had experienced the same loss of body weight as the tumor‐bearing mice. Selective and non‐selective B‐receptor blockade and surgical removal of interscapular brown fat before tumor implantation did not influence the nutritional state of freely‐fed tumor‐bearing mice. Injections of noadrenaline caused a proportionately lower increase in oxygen uptake in tumor‐bearing animals than in freely‐fed controls. Exposure to cold (+5° C) doubled food intake and led to hypertrophy of brown fat in both sarcoma‐bearing mice and control animals. Tumor growth was lower although not statistically different in animals housed at +5°C compared with animals housed at +25°C. It is concluded that brown adipose tissue from sarcoma‐bearing mice could not account quantitatively for the host wasting in tumor‐bearing mice housed at room temperature.
Establishment of a new myeloid leukemia cell line (TK‐1), and isolation of cells having a translocation involving a band 17q23
Authors: Ohno Hitoshi , Doi Shoichi , Fukuhara Shirou , Yamasowa Michihiko , Kannagi Mari , Ishikura Hiroto , Nishikori Masaru , Uchino Haruto
Published: February 2007

A myeloid leukemia cell line (TK‐1) was established from the peripheral blood of a patient with lymphoblastic lymphoma whose leukemia cells were composed of T‐lymphoblasts and immature myeloid cells. The established TK‐1 cell line consisted of immature myeloid cells with heavy azurophilic granulation in the cytoplasm. The TK‐1 cells were positive for peroxidase, and exhibited a strong positive reaction for α‐naphthyl acetate esterase and naphthol AS‐D chloroacetate esterase. The cells were weakly positive for Fcγ‐receptors, showed no phagocytosis and did not reduce NBT. With the treatment of 1α, 25‐dihydroxy‐vitamin D3, they exhibited morphological and functional differentiation. The TK‐1 cell line contained normal diploid cells and pseudodiploid cells, and the two populations were successfully cloned; the clone with a normal karyotype was designated the TK‐1D cell line, and the clone with a pseudodiploid karyotype, which had a translocation involving chromosomes 14, 17 and one other chromosome, was designated the TK‐1B cell line. These cloned cells lacked Epstein‐Barr virus nuclear antigens and had almost the same myelomonocytic characteristics as the parent TK‐1 cells. The breakpoint of chromosome 17 involved in the translocation of the pseudodiploid cells was identified to be a band 17q23.
Transformation of hamster spleen lymphocytes by human T‐cell leukemia virus type I
Authors: Akagi T. , Takata H. , Ohtsuki Y. , Takahashi K. , Oka T. , Yano S. , Miyoshi I.
Published: February 2007

Co‐cultivation of spleen cells of Syrian golden hamsters with lethally irradiated MT‐2 cells harboring human T‐cell leukemia virus type I (HTLV‐I) resulted in the establishment of lymphoid cell lines, HCT‐1 and HCT‐2, which exhibited the normal karyotype of golden hamsters. Cells of both the HCT‐1 and HCT‐2 lines lacked surface immunoglobulins and reacted with a monoclonal antibody (MAb) specific for hamster T cells. Some were positive for OKIal. None of them expressed HTLV structural antigens (p19 and p24) or virus particles, but they contained HTLV‐1 proviral DNA monoclonally. By immunochemical analysis of the labelled cell antigens, sera from adult T‐cell leukemia (ATL) patients reacted with the two polypeptides, p37 and p40, which may not be viral structural proteins and still remain to be characterized. HCT‐1 and HCT‐2 cells were transplantable into newborn hamsters, pre‐treated with anti‐hamster thymocyte serum and non‐treated, respectively, producing diffuse malignant lymphoma. These findings indicated that HTLV‐1 not only immortalized but also transformed hamster T cells non‐productively.
Interaction of recombinant interferons with recombinant interleukin‐2: Differential effects on natural killer cell activity and interleukin‐2‐activated killer cells
Authors: Brunda Michael J. , Tarnowski Deborah , Davatelis Viveca
Published: February 2007

The ability of recombinant interferons (IFNs) to modulate recombinant interleukin‐2 (rIL‐2) augmentation of natural killer (NK)‐cell activity and to modulate the generation of activated killer (AK) cells was examined. Incubation of murine spleen cells for 18 hr with either human rIL‐2 or a human hybrid recombinant IFN alpha, rHuIFN‐αA/D, which is active on murine cells, resulted in a dose‐dependent increase in NK activity; however, recombinant murine IFN gamma, rMuIFN‐γ, had little activity. A more than additive augmentation of cytotoxicity was obtained when spleen cells were incubated with the combination of rIL‐2 and rHuIFN‐αA/D. Incubation of murine spleen cells with rIL‐2 for 3 days resulted in a dose‐dependent induction of AK cells which were cytotoxic to an NK‐resistant tumor target cell. In contrast to the results observed on NK activity, incubation of spleen cells with rHuIFN‐αA/D and rIL‐2 inhibited AK‐cell activity. Partially purified murine IFN‐α had inhibitory activity comparable to that of rHuIFN‐αA/D. The addition of rHuIFN‐αA/D at the initiation of culture of spleen cells with rIL‐2 (day 0) resulted in maximal inhibition of cytotoxicity; inhibition was reduced or absent if rHuIFN‐αA/D was added on day 1 or 2 of culture. The proliferation of spleen cells incubated with rIL‐2 was also inhibited by rHulIFN‐αA/D. Addition of rMuIFN‐γ to spleen cells and rIL‐2 increased the cytolytic activity of AK cells and did not inhibit rIL‐2‐induced proliferation of spleen cells. Similar data were also obtained with human peripheral blood lymphocytes and recombinant cytokines. Incubation of human peripheral blood lymphocytes with rIL‐2 and recombinant human IFN‐α (rHuIFN‐αA) or recombinant human IFN‐γ (rHuIFN‐γ) resulted in a more than additive increase in NK activity. Human AK‐cell cytotoxicity was inhibited by rHuIFN‐αA but enhanced by rHuIFN‐γ. Thus recombinant IFNs have differential effects on rIL‐2‐induced cytotoxic cells, resulting in augmentation or inhibition of activity, which is dependent on both the type of IFN and the cytotoxic activity examined. These results may have important implications for the potential therapeutic use of combinations of these cytokines.
in vitro studies with melphalan and pediatric neoplastic and normal bone marrow cells
Authors: Worthington‐White Diana A. , Graham‐Pole John R. , Stout Susan A. , Riley Christopher M.
Published: February 2007

Chemotherapeutic agents are used in increasingly high dosages to treat patients with refractory cancers. An in vitro clonogenic assay was used to investigate the effects of melphalan on cultures of human neuroblastoma, Ewing's sarcoma, and osteosarcoma cells, as well as on normal bone marrow cells. A I‐hr incubation with 10−5 m melphalan significantly inhibited tumor colony growth of both fresh neuroblastoma and osteosarcoma cells (p < 0.01) while Ewing's sarcoma cells and normal bone marrow appeared resistant to melphalan even at a 100‐fold higher concentration. Incubation with melphalan for 8 hr did not significantly increase the sensitivity of neuroblastoma and osteosarcoma or the relative resistance of Ewing's sarcoma cells; however, normal bone marrow which had remained resistant to melphalan after I hr of incubation, showed significant inhibition of colony growth after an 8‐hr incubation with the agent. Repeated exposure to melphalan increased the degree of inhibition of both tumor and normal marrow colonies. Fresh neuroblastoma cells were significantly more sensitive than long‐term cultured neuroblastoma cells at all drug doses tested. HPLC studies demonstrated that the loss of melphalan followed first‐order kinetics with a half‐life of 69 min, and that in addition to the 2 known breakdown products, mono‐ and dihydroxymelphalan, several other peaks were present which were not attributable to the tissue culture medium or the buffer solutions.
Lung cancer risk associated with cigar and pipe smoking
Authors: Benhamou Simone , Benhamou Ellen , Flamant Robert
Published: February 2007

A case‐control study of 1,529 histologically confirmed male lung cancer cases and 2,899 controls matched for sex, age, hospital of admission and interviewer was conducted in France between 1976 and 1980. The results presented concern the effects of smoking habits, especially cigar and pipe use, on the occurrence of lung cancer, in a total of 38 exclusive cigar smokers, 61 exclusive pipe smokers and 586 mixed tobacco smokers. Exclusive cigar or pipe use (RR = 5.6 and 1.6 respectively) has been shown less harmful than exclusive cigarette smoking (RR = 13.3), mixed cigar and cigarette smoking (RR = 8.5) and mixed pipe and cigarette smoking (RR = 8.0). Different inhalation practices were observed according to smoking habits: while among exclusive cigarette smokers 29.8% never inhaled the smoke, among exclusive cigar and exclusive pipe users these percentages were 89.5% and 86.9 respectively. No significant increase with greater exposure to cigar was found among mixed cigar and cigarette smokers after adjustment for exposure to cigarettes, defined by duration and daily consumption of cigarettes (RR = 1.20), and by type of cigarettes smoked–light or dark, filter or nonfilter (RR = 1.13). Similar results were observed among mixed pipe and cigarette smokers after adjustment for cigarette exposure (RR = 0.95 and 1.04).
Occurrence of a fetal fibroblast phenotype in familial breast cancer
Authors: Schor S. L. , Haggie J. A. , Durning P. , Howell A. , Smith L. , Sellwood R. A. S. , Crowther D.
Published: February 2007

We have previously shown that fetal and adult human skin fibroblasts display distinctive migratory phenotypes when cultured on 3‐dimensional collagen gels in vitro. In the present study, we have used this information to assess the migratory behavior of fibroblasts obtained from patients with either benign or malignant breast disease, and correlated this with the presence of a family history of breast cancer. We have observed that fibroblasts from 17/34 patients with no previous family history of breast cancer displayed fetal‐type behavior in our assay system; in contrast, fibroblasts from 15/16 patients with a positive family history of breast cancer behaved abnormally. This apparently increased probability of expressing a fetaltype migratory phenotype in the patients with a family history is statistically significant (p > 0.008). Skin fibroblasts obtained from 2 healthy and unaffected first‐degree relatives (one male and one female) of patients with a family history of breast cancer also exhibited a fetal‐type migratory phenotype.
A case‐control study of dietary factors and stomach cancer risk in Poland
Authors: Jedrychowski W. , Wahrendorf J. , Popiela T. , Rachtan J.
Published: February 2007

We report results from a case‐control study on stomach cancer conducted in 1980–81 in Cracow, Poland, where the risk of this disease is among the highest reported world‐wide. One hundred and ten cases from a surgical clinic were matched by age and sex to the same number of controls from the same hospital. A matched series from a population‐based health survey was also considered. After adjusting for residency, smoking and various food items, cases and hospital controls showed significant differences in consumption of fruits (RR rarely vs. daily: 3.24; 95% Cl: 1.56–6.77), joint consumption of vegetables, salads and fruits (RR low vs. high: 4.23; 95% Cl: 1.41–12.63), and consumption of protein‐containing foods (RR low vs. high: 0.23; 95% Cl: 0.08–0.61). Consumption of strong alcoholic beverages on an empty stomach (before breakfast) was associated with an RR of 2.09 (1.04–4.22). The findings are discussed in relation to the apparent urban/rural difference in stomach cancer incidence in Poland and the possible underlying etiological factors involved.