bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of different steroid hormones during progression of tumour cells to steroid autonomy
Authors: Darbre Philippa D. , King R. J. B.
Published: February 2007

Progression to steroid insensitivity poses a major problem in therapy of breast cancer, but studies of the origin of steroid‐insensitive cells have been few and have concentrated in any one system on the loss of response to only one steroid. Since both normal and tumour mammary cells have complex endocrine requirements, we wondered how different steroids might interact during loss of steroid sensitivity. Cloned cells from the androgen‐responsive Shionogi 115 mouse mammary carcinoma respond in vitro to both androgens and glucocorticoids in terms of both cellular and molecular parameters but, following prolonged absence of any steroid, these cells become unresponsive. We show here that 2 steroids can interact to prevent the progression to steroid insensitivity since the S115 cells can be protected against any loss of response to either androgen or glucocorticoid with either steroid alone. Androgen protects against loss of glucocorticoid sensitivity and glucocorticoid protects against loss of androgen sensitivity. The clinical implications are discussed.
Estrogen control of lactate dehydrogenase isoenzyme‐5 in human breast cancer
Authors: Nagai M. A. , Sonohara S. , Brintani M. M.
Published: February 2007

Determinations of estradiol receptor (ER), progesterone receptor (PR), total lactate dehydrogenase activity (LDH) and electrophoretic separation of LDH isoenzymes were performed in cytosols from 118 samples of primary infiltrating ductal mammary carcinoma. ER + PR + tumors demonstrated a significant increase in the proportion of the LDH muscle‐type isoenzyme (LDH5) as compared to ER‐PR‐ samples (p < 0.002). Tumors lacking one of the receptors presented intermediate LDH5 percentages. As total LDH activity bore no relation to either the presence or absence of receptors, the increased proportion represents an absolute elevation of LDH5, suggesting that LDH5 may be a promising hormone‐dependence marker. As an in vitro model to study whether LDH5 was induced by estradiol via ER, we have used two human breast cancer cell lines, MCF‐7 and T47D. In both cell lines LDH5 was the sole isoenzyme. Total ER and PR have been determined by a whole‐cell method, in MCF‐7 cells (with high ER levels), after incubation with 10−10 m estradiol, maximal induction of LDH had already been achieved. In relation to T47D (low ER levels) estradiol did not evoke an induction of LDH5 at any concentration examined. In MCF‐7 cells, the level of LDH5 induction paralleled processing of ER. The processing effect was rapid, beginning within 5 min of estradiol addition, and was completed within 1 hr. With 10−6 m tamoxifen, LDH5 induction was suppressed and this effect was reversed by estradiol. Such antiestrogenic effects of tamoxifen on LDH5 have not been observed in T47D cells. Agonistic effects of low doses of tamoxifen on LDH5 were not observed. Our studies suggest that estrogen stimulation of LDH5, involves ER.
Hepatocellular carcinoma: Clinical, aetiological and pathological features in British patients
Authors: Dunk Arthur A. , Spiliadis Haris , Sherlock Sheila , Fowler Martin J. F. , Monjardino Jon P. , Schruer Peter J. , Thomas Howard C.
Published: February 2007

We have examined the clinical, prognostic, aetiological and pathological features of 41 consecutive British patients with hepatocellular carcinoma (HCC). Presenting symptoms were often vague, and patients were generally in poor condition at diagnosis, 56% being of WHO grade 2 performance score or higher. Ascites (46%) and jaundice (35%) were often present at diagnosis, and the median duration of survival from diagnosis was only 6 weeks. Only initial performance grade (p<0.0001) and serum bilirubin concentration (p = 0.02) significantly affected prognosis. Serum alphafoetoprotein (AFP) was positive by counter‐immune electrophoresis in only 34%, but increased to 68% when radioimmunoassay was used. Cirrhosis was present in 33 patients (80%) and was most often cryptogenic (12) or alcoholic (7) in origin. Serum HBsAg was detected in 5 patients (12%) and, of the remainder tested, 21 % had serological evidence of past HBV exposure. None of 8 serum HBsAg‐negative tumour specimens had detectable HBV‐DNA integration into the tumour cell genome. Liver‐cell dysplasia was noted in 56% of patients with liver biopsies predating the diagnosis of HCC, and in 78% of biopsies taken at the time of HCC diagnosis. The commonest histological pattern was trabecular (71%). Other forms were rare; the fibrolamellar pattern was only seen in 2 patients.
Mutation analysis of the N‐ras proto‐oncogene in active and remission phase of human acute leukemias
Authors: Senn H.‐P. , Trǎn‐Thang Ch. , Wodnar‐Filipowicz A. , Jiricny J. , Fopp M. , Gratwohl A. , Signer E. , Weber W. , Moroni Ch.
Published: February 2007

DNA isolated from blood or bone‐marrow samples from 18 patients with acute non‐lymphocytic leukemia (ANLL) and 14 patients with acute lymphocytic leukemia (ALL) was analyzed for the presence of mutations in the N‐ras gene. Using synthetic oligonucleotide probes we detected mutations in 5 cases of ANLL; 4 GGT → GAT transitions in codon 12 and one CAA → AAA transversion in codon 61. One case exhibited homozygosity for the mutation. No mutations could be detected at these codons in the DNA of the 14 ALL patients. In a follow‐up study with 3 of the above 5 patients, the mutation could no longer be detected in 2 cases following successful induction of clinical remission by chemotherapy. However, the mutated N‐ras persisted in one patient who did not achieve remission. We show that oligonucleotide hybridization is a sensitive assay for the detection of N‐ras point mutations, which in ANLL could be used to follow the fate of the leukemic clone during (and after) therapy.
Establishment and characterization of a new human bladder cancer cell line showing features of squamous and glandular differentiation
Authors: Russell Pamela J. , Jelbart Margaret , Wills Edward , Singh Sardool , Wass Jane , Wotherspoon John , Raghavan Derek
Published: February 2007

Tumour‐cell heterogeneity has been studied in a continuous cell line, UCRU‐BL 17CL, established from a xenografted human primary bladder carcinoma. The cell line, grown in vitro for more than 30 generations, reflects the pathology of both the xenograft from which it was derived and the original human tumour. It comprises mainly adenocarcinoma cells which secrete mucin in vitro, as well as squamous and transitional carcinoma cells. Features of both adenocarcinomatous and squamous differentiation have been observed within the same cell. The line expresses ABH blood group isoantigens, binds to peanut lectin and reacts with monoclonal antibodies (MAbs) raised against keratin and against normal and malignant epithelial cells. It also reacts with MAbs against ras p21 proteins and the epidermal growth factor receptor (EGFR). It shows high levels of lactic acid dehydrogenase jsozyme 5, consistent with a high‐grade tumour, forms colonies in meth‐ylcellulose and is tumorigenic in nude mice. The karyotype (human) shows many marker chromosomes, consistent with expression of EGF receptors and ras p21 proteins, and an 11:13 translocation. DNA content, as studied by flow cytometry, reveals a shift from tetraploid to near triploid. This line may provide a useful model for studies of the histogenesis of bladder cancer and the relationship between transitional‐cell carcinoma and the other histological subtypes of this disease.
Burkitt's lymphoma cell lines reveal different degrees of tumorigenicity in nude mice
Authors: Gurtsevitch V. E. , O'Conor G. T. , Lenoir G. M.
Published: February 2007

A quantitative in vivo assay for evaluating the tumorigenicity of Burkitt's lymphoma (BL) cell lines in nude mice is described. It is based on the dose‐response kinetics of BL cell tines in pre‐irradiated (480 rad) nude mice following the s.c. injection of 4 different cell doses. This model system was used to estimate the xenografting potential of 26 BL cell lines derived from BL patients of different geographic and ethnic origins, as well as lymphoblastoid cell lines (LCLs) established by Epstein‐Barr virus (EBV) immortalization of normal B lymphocytes. The results indicate that most BL cell lines are tumorigenic, but LCLs fail to produce progressively growing tumours in nude mice. However, BL cell lines revealed individual degrees of tumorigenicity and accordingly could be divided into 4 groups with high, moderate, low or no tumorigenicity. Preliminary attempts to correlate the xenografting phenotype of BL lines with other characteristics indicate that: (1) the aberrations of chromosome I are more often encountered in cell lines with high and moderate tumorigenicity; (2) EBV‐positive BL lines do nat reveal a higher tumorigenic phenotype in comparison with EBV negative ones; (3) cell lines carrying translocations t(8;22) and t(2;B) might fall more frequently in the group of lines with high and moderate tumorigenicity; and (4) when LCLs grow in nu/nu mice, rejection always occurs and is associated with massive tumour necrosis. These findings suggest that the tumorigenicity of BL cell lines in immunosuppressed animals is nat related with EBV, but with certain chromosomal abnormalities (BL‐specific and nonspecific) indicating that this in vivo model system can be instrumental for the identification of other factors or stages involved in BL development.
Antibody targeting to the murine lymphoma ESb‐MP: Increased accumulation due to reduced internauzation into lymphoma cells as compared to normal lymphoid cells
Authors: Matzku S. , Kirchgessner H. , Schirrmacher V.
Published: February 2007

Using rat monoclonal antibody (MAb) (2–;15A against the spontaneously metaxtasizing mouse lymphoma variant ESb‐MP, we elaborated conditions for targeting. In vitro, high binding of labelled antibody to ESb‐MP cells and low binding to Iymphoid cells (e.g., spleen cells) was noted. In vivo, we observed pronounced accumulation in spleen, lymph nodes and bone marrow, the uptake kinetics indicating high accessibility of the target antigen in these tissues, and rapid clearance of radioactivity from blood and most normal tissues, indicating degradation of the antibody and excretion of the label. Binding to lymphoma tissue was slow but persistent, resulting in high tumor:tissue ratios only after 2–3 days. Biodistribution could be dramatically changed by pre‐treatment of animals with excess cold antibody, which reduced trapping of labelled antibody in normal lymphatic tissue, leading to prolonged persistence in the blood and preferential uptake into tumor tissue. Monovalent 12–15A fragments showed less pronounced binding to lymphatic tissue, while being rapidly cleared from the circulation by virtue of their inherent tendency to bind to kidney tissue. Tumor:tissue ratios up to 56:1 were obtained by a combination of pre‐treatment with unlabelled 12–15A IgG or Fab fragment, followed by injection of labelled fragment or IgG, respectively. This is interpreted on the basis of differences in the internalization and retention of antigen‐antibody complexes. Pre‐treatment obviously leads to a temporary blockade or removal of the target antigen, which is much more efficient with normal lymphoid cells than with tumor cells. Thus, it may become possible to target antibodies into the tumor despite concurrent antigen expression on normal tissue.
Formation of dna adducts and water‐soluble metabolites of benzo[a]pyrene in human monocytes is genetically controlled
Authors: Nowak Dennis , Schmidt‐Preuss Ute , Jörres Rudolf , Liebke Frank , Rüdiger Hugo W.
Published: February 2007

Formation of DNA adducts and of water‐soluble metabolites was studied in monocytes of 86 first‐degree relatives of 15 families. Tests were performed with blood monocytes using (G‐3H)‐benzo[a]pyrene as a model pro‐carcinogen. Variance analysis revealed significantly higher inter‐familial than intra‐familial variations. From these data we conclude that the formation of DNA adducts is genetically controlled. Therefore the enhanced formation of benzo[a]pyrene DNA adducts in lung cancer patients found in earlier studies may reflect a genetic predisposition for lung cancer in some patients.
P53 expression in breast cancer
Authors: Cattoretti Giorgio , Rilke Franco , Andreola Salvatore , D'Amato Lucia , Delia Domenico
Published: February 2007

Immunohistochemical evaluation of 200 primary breast cancers with the anti‐p53 mouse monoclonal antibody (MAb) PAb421 showed positivity in nuclei of malignant cells in 31 cases (15.5%). PAb421+ cases were significantly more frequently epidermal growth factor receptor (EGF‐R)‐positive (67.7%; p < 0.001) and estrogen receptor (ER)‐negative (73.3%; p < 0.001); they displayed surface histocompatibility class‐1 (80.6%; p < 0.01) and II (74.2%; p < 0.05) antigens. Low values for progesterone receptor (mean 67.20 ± 25.2 fmol/mg; p < 0.05) and a high number of cells positive for the proliferationassociated antigen Ki‐67 (log mean 6.88 ± 0.33; p < 0.01) were found in PAb421+ tumors as well as a high number of grade‐3 infiltrating duct carcinomas (70%; p = 0.01). Of the 200 cases of mammary carcinoma, 88 were further analyzed using another human specific anti‐p53 MAb PAb1801, and 40 (45.5%) were found positive. This MAb stained all the PAb421+ cases and was significantly associated with negative ER status (39.5%; p < 0.05) and high Ki‐67 scores (log mean 6.93 ± 0.24; p = 0.001). Analysis of PAb1801+/Pab421− cases for HLA antigens, EGF‐R and ER showed a phenotype similar to that of the p53−ve/ER+ carcinomas, except for the high Ki‐67 score. No differences in age of the patient, number of involved nodes, tumor size, ploidy or labelling index scores were evident between p53+ and − carcinomas. We concluded that p53 in mammary carcinomas is associated with ER‐negative, growth factor receptor‐positive, high‐grade tumors, and is a promising new parameter to evaluate the cellular biology and prognosis of breast cancer.
Estimates of the worldwide frequency of sixteen major cancers in 1980
Authors: Parkin D. M. , Läärä E. , Muir C. S.
Published: February 2007

The numbers of new cancer cases in 16 common sites occurring in 1980 have been estimated for 24 areas of the world for which the United Nations produces population estimates. For the world as a whole, the total number of new cases was 6.35 million, almost exactly evenly divided between the developed and developing countries. In males, the most important sites were lung, stomach, colon/rectum, mouth/pharynx, prostate and oesophagus, and in females breast, cervix, colon/rectum, stomach, corpus uteri and lung. When the two sexes are combined, stomach cancer emerges as the most common cancer in 1980 (669,400 new cases per year), but this estimate is only slightly greater than that of lung cancer (660,500 new cases), and comparisons with earlier estimates for 1975 suggest that, with declining incidence rates for stomach cancer and the continuing rise for lung cancer, the latter would become the most common cancer in the world by the end of 1981. The implications for cancer control in the developed and developing countries of the world are discussed.
Monoclonal antibodies against mesothelial membrane antigen discriminate between malignant mesothelioma and lung adenocarcinoma
Authors: Stahel Rolf A. , O'Hara Carl J. , Weibel Robert , Martin Alexander
Published: February 2007

Monoclonal antibodies (MAbs) were generated by immunizing mice with the mesothelioma cell line SPC111 and selected by indirect immunofluorescence on viable cells. Indirect immunofluorescence staining and radioimmunoassays demonstrated selective binding of the antibodies ME1 and ME2 with the surface membrane of mesothelioma, but not with lung adenocarcinoma cell lines. Lung small‐cell carcinoma cell lines were unreactive, while staining was seen in a proportion of lung squamous‐cell carcinoma cell lines. The antibodies were unreactive with other cell lines, including breast, colon, ovarian, and renal‐cell carcinoma, leukemia, and lung fibroblast. The antibodies stained normal mesothelial cells, but were unreactive with normal bronchial epithelial cells in primary cultures, or peripheral blood cells. Immunohistochemical staining of cryostat sections of tumor tissues confirmed the ability of the antibodies to distinguish between mesothelioma and lung adenocarcinoma. All 12 mesothelioma tissues, but none of 9 lung adenocarcinomas or large‐cell carcinomas, stained with the MAbs. Staining of malignant mesothelioma tissues was very homogeneous. Some lung squamous‐cell carcinomas and breast carcinomas were stained focally by both, and some ovarian carcinomas by one antibody. Solid‐phase radioimmunoassays demonstrated antigen sensitivity to chymotrypsin digestion and binding competition between the antibodies. The antibodies ME1 and ME2 identify a surface membrane antigen with preferential expression on normal and malignant mesothelial cells. They distinguish malignant mesothelioma from lung adenocarcinoma on cryostat sections and promise to be useful tools in biological studies of mesothelial cells.
Evidence for alpha‐melanocyte‐stimulating hormone (α‐MSH) receptors on human malignant melanoma cells
Authors: Ghanem G. E. , Comunale G. , Libert A. , Vercammen‐Grandjean A. , Lejeune F. J.
Published: February 2007

The presence of α‐MSH receptors on human melanoma has so far been suggested in the literature but not proved. We describe a reproducible and specific binding assay of α‐MSH on human melanoma cells, using a high‐specific‐activity 125I‐labelled hormone (1.5 to 2 mCi/μg) with consistent receptor binding (usually exceeding 2 pg/106cells) and stable for 3 weeks. Asynchronized cells in suspension were incubated for 15 min at 37°C with the tracer and various concentrations of unlabelled hormones. Synthetic α‐MSH was compared to β‐MSH, ACTH1‐24, ACTH4–10, β‐LPH, CLIP, CRF, MIF I, A8VP and β‐endorphin. Out of a panel of 8 human melanoma cell lines, 3 showed specific and reproducible α‐MSH binding curves. No significant binding to human fibroblast and human carcinoma cells was seen. α‐MSH, β‐MSH and, to a lesser extent ACTH4–10 (a part of the α‐MSH sequence) were the only peptides able to displace labelled α‐MSH from its binding sites, indicating the high specificity of the MSH receptor. Affinity constants (Ka) ranged from 108 to 109 I/mole and the estimated receptor number was 1,000 to 2,000 per cell. We conclude that some human melanoma cell lines expressed specific MSH receptors with stable affinity but which are low in number.
Interferon‐gamma treatment of B16 melanoma cells: Opposing effects for non‐adaptive and adaptive immune defense and its reflection by metastatic spread
Authors: Zöller M. , Strubel A. , Hämmerling G. , Andrighetto G. , Raz A. , Ben‐Ze'ev A.
Published: February 2007

The impact of interferon‐gamma (IFN) treatment of tumor cells on non‐adaptive and adaptive immune defense and its reflection by metastatic spread were evaluated using a weakly metastasizing variant of B16 melanoma (B16‐FI). Treatment of B16‐F1 with IFN resulted in a decrease in binding structures for NK cells and concomitantly in augmented metastasizing capacity. In line with this, activation of NK cells and Mo, which led to reduction of metastatic nodes, was less efficient with IFN‐treated B16‐F1, while after elimination of non‐adaptive immune defense, the number of metastases increased significantly, but irrespective of IFN treatment. On the other hand, IFN‐treated B16‐F1 cells became more prone to killing by cytotoxic T‐cells (CTL). This was due to increased lysability by CTL and to increased immunogenicity; i.e., a higher frequency of B16‐specific CTL was observed after immunization with IFN‐treated than with untreated B16‐F1. The reverse phenomenon was observed with anomalous and/or lymphokine‐activated killer cells (AK/LAK). The common cause of increased antigenicity and immunogenicity may reside in increased expression of class‐I and de novo expression of class‐II MHC antigens after IFN treatment. Increased antigenicity and immunogenicity of IFN‐treated B16‐F1 was reflected by significant reduction of metastatic nodes, prolonged survival and increased TD100 in animals immunized with IFN‐treated vs. untreated melanoma cells. Comparison of the divergent effects of IFN treatment on B16‐F1 melanoma cells showed that the benefit of increased antigenicity/immunogenicity clearly out‐weighed the disadvantage of reduced susceptibility to non‐adaptive immune defense.
Biological characterization and oncogene expression in human colorectal carcinoma cell lines
Authors: Trainer Deborah L. , Kline Thomas , McCabe Francis L. , Faucette Leo F. , Feild John , Chaikin Margery , Anzano Mario , Reiman David , Hoffstein Sylvia , Li Dian‐Jun , Gennaro Doris , Buscarino Charles , Lynch Mark , Poste George , Greig Russell
Published: February 2007

To establish well‐characterized cellular reagents for the study of colon carcinoma, we have examined 19 human colorectal carcinoma cell lines with regard to morphology, ultra‐structure, expression of tumor‐associated antigens, proliferative capacity in vitro, anchorage‐independent growth, oncogene expression, tumorigenicity and malignant potential. Cell lines examined were cultured under identical conditions, and in vitro and in vivo analyses were performed in parallel on replicate cultures. Three classes of colorectal cell lines were defined according to their tumorigenicity in nude mice. Class‐I lines formed rapidly progressing tumors in nearly all mice at an inoculum of 106 cells. Cell lines belonging to class‐2 were less tumorigenic, producing tumors later and at a slower growth rate. Class‐3 lines were non‐tumorigenic under all experimental conditions tested. By Northern analysis, the oncogenes c‐myc, H‐ras, K‐ras, N‐ras, myb, fos and p53 were expressed in nearly all cell lines examined. In contrast, transcripts for abl, src and ros were not detected. The best in vitro predictor of tumorigenicity was colony formation in soft agar. There was no detectable correlation between tumorigenicity and metastatic potential, doubling time in vitro, production of tumor‐associated markers, xenograft histology or expression of specific oncogenes.
Dieldrin‐induced changes in isoenzyme composition in the livers of CF‐1 mice
Authors: Van Ravenzwaay Ben , Toussant Hilda J. M. , Schmitt Rolf L.
Published: February 2007

The isoenzyme composition of lactic dehydrogenase (LDH), pyruvate kinase (PK) and alanine‐aminotransferase was determined in the livers of CF‐1 mice exposed to 0, 5 or 10 ppm dieldrin in the diet, over a period of 14 months. This study was carried out to evaluate whether the liver tumor promoter dieldrin advances the biological age of CF‐1 mouse liver. Oral dieldrin exposure induced a dose‐dependent shift towards the fetal types of lactic dehydrogenase and pyruvate kinase, within 1.5 months of initiation of treatment. After the initial shift, no additional dieldrin‐dependent changes were found in CF‐1 mouse liver throughout the experimental observation period. Thus, the initial shifts in isoenzyme composition of LDH and PK appear to reflect the adaptation of the liver to increased functional demands imposed by dieldrin treatment. The expression of the cytoplasmic A‐alanine‐aminotransferase isoenzyme decreased with age in untreated control mice. Dieldrin treatment enhanced this process in a dose‐dependent manner. These data suggest that dieldrin treatment can accelerate age‐dependent changes in gene expression.
Diet and cancer of the stomach: A case‐control study in China
Authors: Hu Jinfu , Zhang Shufen , Jia Ermin , Wang Quoqing , Liu Shude , Liu Yunyuan , Wu Yanping , Cheng Yitang
Published: February 2007

A case‐control study focusing on the role of single food items was undertaken in the Heilongjiang area, 241 patients with histologically verified stomach cancer and an equal number of controls (with non‐neoplastic diseases) matched by age, sex and area of residence being interviewed during a 2‐year period. Questions asked covered economic status, occupation, histories of smoking and drinking, diet and dietary habits and disease history. Data concerning the average frequency and quantity of consumption of single food items were obtained by the same interviewer. An inverse association between the consumption of vegetables and stomach cancer was observed whereas high intake of potatoes and of salted and fermented soya paste appeared to be high‐risk factors. Specifically, Chinese cabbage plays an important role in reducing the risk of developing stomach cancer.
Occupation and lung cancer in two industrialized areas of northern Italy
Authors: Ronco Guglielmo , Ciccone Giovannino , Troia Bruno , Vineis Paolo
Published: February 2007

A population‐based case‐control study on lung cancer was conducted in 2 industrialized areas of northern Italy. Cases (126) were all males who died from lung cancer between 1976 and 1980. Controls (384) were a random sample of males dying from other causes during the same period. Jobs held during working life have been analyzed according to a list of occupations already known to be causally associated with lung cancer (list A) and a list of occupations suspected of being so (list B). Attributable risk percentages in the population for occupations included in either list A or B were about 36% and 12% in the 2 areas. Welders or workers in industries in which welding is common showed elevated odds ratios: 2.9 for welders (95% Cl 0.9–9.8); 4.9 (1.1–22.9) for structural metal workers; 11.4 (2.6–49.9) for workers in structural metal production. Other job categories associated with lung cancer included: electricians and workers in electrical machine production, woodworker (in furniture or cabinet making, but not in carpentry or joinery) and cleaning services. Smoking did not seem to exert a substantial confounding effect. Attributable risk percentages for tobacco smoking were about 78% and 76% in the population of the 2 areas.
Occupation and risk of cancer of the lower urinary tract among men. A case‐control study
Authors: Claude Jenny C. , Frentzel‐Beyme Rainer R. , Kunze Ekkehard
Published: February 2007

Data from a hospital‐based matched case‐control study with 531 male pairs were analyzed for risks of cancer of the lower urinary tract associated with previous employment and particular occupational exposures. Statistically significant odds ratios were obtained for ever‐employment as mining workers (2.0), turners (2.3), tailors (2.7), truck drivers (1.8), locomotive drivers (3.0) and janitors (3.5), whereas odds ratios of 3.0 or more, found for rubber and plastics workers, printing workers, gas workers, artists and chemists were not statistically significant. When adjusted for smoking, there was a trend toward increasing relative risks with increasing duration of employment as truck drivers and as turners, and relative risks rose 3‐fold for 30 or more years of employment. With regard to a priori high‐risk industries, ever‐employment in the rubber, plastics and synthetics, dyestuff and paints, mining, and printing industries and secondary processing was associated with significantly higher relative risks, and a statistically significant trend in risk with increasing duration of employment was found for the first 3 industries mentioned. With regard to job‐related exposures to specified substances, the relative risks observed for increasing duration of exposure suggest that exposures to petroleum, oils, chromium/chromate, spray paints, and zinc, which correspond to exposures involved in the occupations showing a higher relative risk in this study, are associated with a higher risk for cancer of the lower urinary tract.
Loss of alleles on chromosome 18 and on the short arm of chromosome 17 in polyploid colorectal carcinomas
Authors: Monpezat J.‐Ph. , Delattre O. , Bernard A , Grunwald D. , Remvikos Y. , Muleris M. , Salmon R. J. , Frelat G. , Dutrillaux B. , Thomas G.
Published: February 2007

The zygosity of 19 colorectal carcinomas (either near‐diploid or polyploid) from patients known to be heterozygous for RFLPs located on chromosome 18 or on the short arm of chromosome 17 has been examined. In most cases, at least one allele was significantly under‐represented. The reason for the absence of complete loss of heterozygosity was investigated for 5 polyploid tumors. It was shown that the diploid component which, in these tumors, is essentially composed of non‐neoplastic cells, remains heterozygous as the polyploid component invariably loses heterozygotity. The results strongly suggest that many colorectal carcinomas originate from a single cell which had lost at least part of either chromosome 18 or of one short arm of chromosome 17, or both.
Changes in plasma gangliosides in relation to tumor growth and their tumor‐enhancing effect
Authors: Saha Sandip , Chattopadhyay Utpala
Published: February 2007

Gangliosides in the plasma of Ehrlich ascites turn or‐bearing mice showed changes, both quantitative and qualitative, with progress of tumor. Quantitative changes assessed by chemical estimation indicated a gradual increase of gangliosides up to day 6 of tumor growth followed by a decline leading to a level below the normal by day 12. Qualitative changes studied by thin‐layer chromatography indicated appearance of new gangliosides in the plasma of tumor‐bearing mice, which were absent from normal plasma. One of these gangliosides appears to be of tumor‐cell origin. Gangliosides obtained from tumor‐bearing mouse plasma enhanced tumor growth when adoptively transferred with tumor cells into normal mice.
Qualitative and quantitative differences between Burkitt lymphoma and lymphoblastoid cell lines in the expression of membrane ecto‐nucleotidases and in the response to agonists of the A2‐type adenosine receptor
Authors: Gutensohn Wolf , Jahn Heidi
Published: February 2007

The activity of ecto‐nucleotidases has been determined on intact cells from Burkitt lymphoma (BL) and lymphoblastoid cell lines established in vitro (LCLs). BL cells never express ecto‐5′‐nudeotidase (5′‐N) and exhibit only low levels of ecto‐ATPase activity, whereas LCL‐cells usually express both enzymes to varying degrees. There is a certain correlation (r = 0.75) between 5′‐N and ecto‐ATPase. When cAMP formation in response to agonists of the A2‐typc (stimulating) adenosine receptor is measured in the same cell lines there is no correlation with the expression of ecto‐nucleotidases. Within pairs of BL and LCL cell lines derived from the same donor, 5′‐N inverse relationship between ecto‐nucleotidases and the response to the adenosine receptor agonist N‐ethyl‐car‐boxamido‐adenosine (NECA) is observed. BL cells show a good response to NECA, whereas this is low or absent in LCL cells. Treatment of cells which exhibit both S′‐N and the adenosine receptor with specific polyclonal or monoclonal antibodies against the enzyme does not impair the function of the receptor. Antisera against peptides of the membrane antigen BNLF I‐MA, coded by the EBV‐genome, do not co‐precipitate 5′‐N out of detergent extracts of LCL‐cells. In both cases 5′‐N cannot be closely associated with other membrane components. The differences between BL and LCL cells in ecto‐nucleotidases and the adenosine receptor appear to be fairly stable phenotypical markers, independent of other parameters and suitable for use in distinguishing these cells in all populations.
Family history of colorectal cancer as a risk factor for benign and malignant tumours of the large bowel. A case‐control study
Authors: Bonbllj Luiguu , Martines Hugo , Conio Massimo , Bruzzi Paolo , Aste Hugo
Published: February 2007

The relationship between first degree family history of co‐lorectal cancer and the risk of benign or malignant tumours of the large bowel was investigated in a case‐control study. Two groups of cases (283 patients with adenomatous polyps and 414 patients with adenocarcinoma of the large bowel) and 2 groups of controls (199 polyp‐free subjects and 456 hospitalized patients) were interviewed. Since no difference in the frequency of family history between the 2 control groups was detected, these were lumped together. A 3‐fold increase in risk of adenomatous polyps in relatives of patients with colon cancer was observed (OR = 3.18. 95% Cl 2.06‐4.89). The relative risk of colorectai cancer among relatives of patients with adenocarcinoma was 2.36 (95% Cl 1.54‐3.60). No significant difference in the frequency of first degree relatives with a history of cancer of the large bowel was detected between patients with colorectai cancer and those with adenomatous polyps. When only history of colorectai cancer among parents was considered, the results closely paralleled those of the previous analysis.
Survival patterns for malignant mesothelioma: The seer experience
Authors: Spirtas Robert , Connelly Roger R. , Tucker Margaret A.
Published: February 2007

Statistical analyses of 1,475 histologically confirmed cases of malignant mesothelioma ascertained through the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute for the years 1973‐1984 showed age at diagnosis, sex, stage of disease, type of treatment, and geographic area of residence to be important predictors of patient survival, although type of treatment may be confounded with prognostic factors (patients selected for surgical treatment tended to have better performance status than other patients). Women below the age of 50 had an unusually long survival, even after adjustment for the effects of other variables in the model. A relatively large proportion of female cases had site of disease designated as peritoneum, but site was not a significant prognostic factor. These results suggest that age, gender and stage of disease should be carefully considered in designing and analyzing clinical trials for persons with mesothelioma. Survival was shorter in the 4 SEER registries which had shipbuilding as a major industry than in the others with less potential asbestos exposure, offering weak support for the hypothesis that asbestos‐exposed cases of mesothelioma have worse survival experience than other cases.
Dose Versus pharmacokinetics for predicting tolerance to 5‐day continuous infusion of 5‐FU
Authors: Milano G. , Roman P. , Khater R. , Frenay M. , Renee N. , Namer M.
Published: February 2007

This non‐randomized study reports pharmaco‐clinical data on 5‐FU administered by the widely used 5‐day continuous infusion schedule to 42 patients with metastatic colorectal cancer; 5‐FU was given by hepatic intra‐arterial route (h.i.a.) at doses ranging from 800 to 1,450 mg/m2, and by a systemic intravenous route (i.v.) at doses ranging from 650 to 1,300 mg/m2. 5‐FU blood levels were available for a total of 179 cycles. Toxicity was dose‐de pendent during h.i.a. cycles but not during i.v. cycles. For h.i.a. cycles, 1,000 mg/m2/day represented the threshold dose for tolerance. The individual total cycle drug concentration‐time product might predict toxicity for both i.v. and h.i.a. cycle when the threshold is set at 30,000 ng/ml hr. These data may be of practical value for improving the therapeutic index of 5‐day continuous treatment by 5‐FU given by i.v. or h.i.a. routes.
The copenhagen case‐control study of renal pelvis and ureter cancer: Role of smoking and occupational exposures
Authors: Jbnsen O. M. , Knudsen J. B. , McLaughlin J. K. , Sørensrn B. L.
Published: February 2007

Smoking habits and occupational exposures were investigated for 96 patients with cancer of the renal pelvis and ureter (including papilloma) and 294 hospital controls. In comparison with persons who never smoked, significantly increased relative risks were seen for smokers of cigarettes alone (RR = 2.6; 95% Cl: 1.0‐6.7) and in combination with other types of tobacco (RR = 3.8; 95% Cl: 1.3‐11.5). Non‐signiftcantty increased relative risks were observed for pipe smokers (RR = 2.2; 95% Cl: 0.1‐97) and for mixed pipe, cigar, and cigarillo smokers (RR = 6.S; 95% Cl: 0.4‐21.2). A strong dose‐effect (p<0.001) relationship was seen between the lifetime total amount of tobacco smoked and the risk of pelvis‐ureter tumors, with the heaviest smokers having an 8‐fold risk. Comparison with the dose‐effect relationship for a parallel study of bladder cancer indicated that the relationship with tobacco was stronger for pelvis‐ureter tumors. Deep inhalation of cigarette smoke increased the risk (RR = 3.4; 95% Cl: 1.9‐6.1), while stopping smoking (RR = 0.6; 95% Cl: 0.1‐1.1) and use of filter cigarettes (RR = 0.5; 95% Cl: 0.3‐0.9) decreased the risk. Significantly increased risks emerged for employment in the chemical, petrochemical and plastics industries (RR = 4.0; 95% Cl: 1.6‐9.8), and for exposure to coal and coke (RR = 4.0; 95% Cl: 1.2‐13.6), asphalt and tar (RR = 5.5; 95% Cl: 1.6‐19.6). Cigarette smoking accounted for 56% of male and 40% of female pelvis and ureter tumors in eastern Denmark.
Inflammatory cell infiltrates in human melanoma at different stages of tumor progression
Authors: Bröcker E. B. , Zwadlo G. , Holzmann B. , Macher E. , Sorg C.
Published: February 2007

Progression of human melanoma is associated with changes in antigenic phenotypes of tumor cells. To establish whether inflammatory infiltrates in progressing melanoma also change, we studied 146 cutaneous melanomas at different stages of progression. Monoclonal antibodies (MAbs) against lymphocyte and macrophage subpopulations, interteukin‐2 receptor (IL‐2 R), immune interferon (IFN‐γ), and the IFN‐γ‐inducible, progression‐associated melanoma antigens HLA‐DR and gp89 were applied in situ. During the course of melanoma progression, decreased amounts of peri tu moral T cells, IL‐2 R‐ex‐pressing lymphocytes and dermal T6+ dendritic cells were found, while increased numbers of intraiumoral T cells, inflammatory (27E10+) and mature (25F9+) macrophages were associated with local progression of primary melanomas. In metastases, most infiltrate components except 25F9+ macrophages were rare. Positive correlations were observed between: (1) dermal T6+ cells and IL‐2 R+ lymphocytes, and (2) presence of IFN‐γ in the infiltrate and HLA‐DR and gp89 antigens on tumor cells. In all stages, HLA‐DR expression on tumor cells was correlated with: (1) a shift towards T8+ lymphocytes in the infiltrates and (2) a loss of IL‐2 R expression. Our data suggest mutual influences between melanoma cells and mononudear cell infiltrates in situ.
Marker polypeptide differences between spontaneous strongly and weakly metastatic cancer cells identified by 2‐dimensional gel electrophoresis
Authors: Grimstad Ivar Amund , Thorsrud Anne Karine , Varani James , Ward Peter A. , Jellum Egil
Published: February 2007

A recent 2‐dimeniional gel electrophoresis study revealed several polypeptide differences between a strongly metastatic and a weakly metastatic clone from a single chemically induced murine fibrosarcoma (Jellum et al., 1984). To exclude the possibility that this was merely coincidental, the study is extended here to 2 other fibrosarcomas recently and similarly induced in mice of the same inbred strain. Metastatic potential was defined by the number of lung metastases spontaneously formed from a transplanted primary footpad tumor. One strongly (or moderately) metastatic cell line and I weakly metastatic line from each of the 3 fibrosarcomas were examined in the same experiments. In confirmation of our previous results, the same poiypeptides consistently occurred in considerably greater amounts in the weakly metastatic than in the strongly metastatic cells. One of these marker polypeptides was absent from the strongly metastatic cell lines. In comparison with 2 of the 3 most metastatic lines, the third line was only moderately metastatiC., and differed least strongly from the 3 weakly metastatic cell lines with regard to expression of the marker polypeptides. Marker polypeptide expression showed no consistent correlation with tumorigenicity. No other consistent polypeptide differences between strongly metastatic and weakly metastatic cells could be identified among the approximately 2,000 cellular polypeptides separated on the gels.
Amplification of endogenous proviral MuLV sequences in radiationinduced osteosarcomas
Authors: Strauss P. Günter , Schmidt Jörg , Pedersen Lene , Erfle Volker
Published: February 2007

The endogenous ecotropic provirus of BALB/c mice was found to be amplified in 17 out of 29 radiation‐induced osteosarcomas. In contrast, 19 clonal cell lines established from bone‐marrow cells of a tumor‐bearing mouse, which were used as controls, did not reveal newly acquired ecotropic proviruses. Ecotropic viral RNA was expressed in tumors that showed reintegrated proviruses. DNA probes from 2 tumors, derived from cellular sequences flanking the newly integrated proviruses, did not detect DNA rearrangements in any of the other tumors. The possible role of activated endogenous retroviruses in the development of radiation‐induced osteosarcomas is discussed.
Quantitative determination of water‐soluble scavengers in neoplastic and non‐neoplastic human breast tissue
Authors: Honegger C. G. , Torhorst J. , Langemann H. , Kabiersch A. , Krenger W.
Published: February 2007

The water‐soluble scavengers ascorbic acid (Asc), cysteine (Cys), glutathione (GSH) and uric acid (UA) as well as DNA content were determined in 40 breast tissue samples (neoplastic and non‐neoplastic tissues from 20 patients). To allow proper homogenization to take place, a fixed number of sections was cut from a tissue cylinder of known diameter. Adjacent sections were stained with hematoxylin‐eosin and the fractions of epithelium, fat and connective tissue were estimated as a percentage of the section area. Protein‐free extracts were injected into a reverse‐phase high‐pressure liquid chromatography system and scavengers quantified with 2 electrochemical detectors (gold and glassy carbon). DNA and all scavengers, except UA, were greatly increased in cancer tissues in nearly all cases. Amounts of Asc and GSH in neo plastic tissue correlated closely with DNA values and percentage of epithelium, those of Cys not so closely and those of UA not at all. We assume that Asc and GSH were located mainly in the epithelium, UA mainly in the extracellular space and Cys in both spaces. When values were expressed as μmol/g DNA, a parameter related to content per cell, values were higher in neoplastic than in non‐neoplastic tissue for Asc (18/ 20 cases), GSH (17/20) and Cys (14/20) and lower in neoplastic tissue for UA (19/20). It is known that increased GSH protects cells against certain drugs in tissue cultures. For in vivo treatment the presence of increased Asc (and to a lesser extent Cys) in addition to GSH could be of importance.
Smooth‐muscle differentiation in stromal cells of malignant and non‐malignant breast tissues
Authors: Sappino A.‐P. , Skalli O. , Jackson B. , Schürch W. , Gabbiani G.
Published: February 2007

A mouse monoclonal antibody (MAb) recognizing α‐smooth‐muscle actin has been used to study smooth‐muscle differentiation features in the stromal cells of desmoplastic reactions accompanying mammary tumors. We have studied, by the same immunohistochemical technique, a series of malignant and non‐malignant human breast tissues. Cells composing the desmoplastic reaction were found to express α‐smooth‐muscle actin in all the 11 breast carcinomas examined, whereas no immunostain was demonstrated in the stromal cells of 7 breast tissue samples histologically defined as normal. Three of 9 cases of fibrocystic disease showed a minority of positively stained stromal cells, generally in association with epithelial hyperplasia. All the 7 cases of sclerosing adenosis, 3 of 4 cases of diffuse papillomatosis and all 3 intraductal papillomas exhibited a majority of immunoreactive stromal cells. Numerous stromal cells in 3 of 11 circumscribed fibroadenomas analyzed expressed low amounts of α‐smooth‐muscle actin. The factor(s) responsible for smooth‐muscle differentiation in stromal cells are presently unknown, but the detection of this previously unsuspected stromal cell phenotype in non‐malignant mammary tissues might help in characterizing the variant morphological aspects designated under the label “fibrocystic disease” and in understanding the biology of pre‐malignant or early malignant lesions of the breast.
Transplantation of human breast epithelia to mammary‐gland‐free fat‐pads of athymic nude mice: Influence of mammotrophic hormones on growth of breast epithelia
Authors: Sheffield Lewis G. , Welsch Clifford W.
Published: February 2007

Normal human breast tissue was enzymatically dissociated and the cells were injected Into the gland‐free fat‐pads of athymic nude mice. Within 30 days, small, spherical, duct‐like epithelial elements (organoids) formed in 68% of the fat‐pads inoculated (0‐23 organoids/fat‐pad). Short‐term (30‐day) treatment of the host mice with mammotrophic hormones [secretions from a choriunic, somato‐mammotrophin‐secreting transplantable human choriocarcinoma (JEG‐3), secretions from a prolactin‐ and growth‐hormone‐secreting transplant‐able rat pituitary tumor (GH3), estrogen and/or progesterone] and/or cAMP inducers (cholera toxin) significantly (p<0.05) increased the size of the human breast organoids but did not increase organoid number or induce extensive and expansive growth (extensive duct elongation and branching) of these structures. Such treatments induced intense proliferation of the host mouse mammae resembling that which occurs during late pregnancy. The results of this study, therefore, provide evidence that normal human breast epithelium can be readily accepted by and maintained in the gland‐free fat‐pad of the athymic nude mouse, and the epithelium, within 10 days, forms spherical duct‐like structures (organoids). The human breast organoids are hormone‐responsive, as they respond to a mammotrophic growth stimulus by an increase in size. The failure of the human breast organoids to grow expansively in the gland‐free fat‐pad of this immunologically deficient mouse does not appear to be due to the absence of an appropriate hormonal growth stimulus.
Risk factors for cancer of the renal parenchyma
Authors: McCredie Margaret , Ford Joyce M. , Stewart J. H.
Published: February 2007

A case‐control study of cancer of the renal parenchyma (360 cases and 985 controls) investigated lifestyle and dietary risk factors by means of a questionnaire survey. A lifetime history concerning urological disease and consumption of analgesics, tobacco, and prescribed medicines, was obtained together with current dietary and demographic information. Estimates of relative risk were calculated using logistic regression. Statistically significant associations were found with phenacetin‐containing analgesics, urological disease and increasing consumption of milk. No association was found with consumption of aspirin, paracetamol, prescribed medicines, tea, coffee or animal proteins other than milk, or with the type of fat or oil used for cooking or spreading. The association with tobacco just failed to reach significance.
Fluid intake and bladder cancer in UTAH
Authors: Slattery Martha L. , West Dee W. , Robison Linda M.
Published: February 2007

A population‐based, incident case‐control study was conducted in Utah to assess the relationship between fluid intake and bladder cancer. Cancer cases (n = 419) were identified through the Utah Cancer Registry, and controls (n = 889) were obtained through random digit dialling and the Health Care Financing Administration. After adjustment for cigarette smoking, age, sex, history of diabetes, and history of bladder infections using multiple logistic regression analysis, total fluid intake was not found to be related to bladder cancer development. Specific fluids related to bladder cancer risk were milk intake (OR = 0.64) and caffeinated coffee intake (OR = 1.60). A linear trend for a dose‐response protective effect was observed for milk, while coffee increased risk only when 40 or more cups were consumed per week. Alcohol increased risk only when consumed at high levels (over 3.64 ounces or 103 g per week) by people who never smoked cigarettes (OR = 2.37). Likewise, tea consumption in non‐cigarette smokers increased bladder cancer risk (OR = 2.25). Results from this study suggest that types of fluids consumed may play a role in the development of bladder cancer. Furthermore, it is hypothesized that the dietary components of these beverages may be related to the development of bladder cancer.