bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival of breast‐cancer patients and body size indicators
Authors: Kyogoku Shinji , Hirohata Tomio , Takeshita Setsuko , Nomura Yasuo , Shigematsu Takao , Horie Akio
Published: February 2007

The association of breast‐cancer survival with various risk factors was investigated using data of 213 breast‐cancer patients who underwent surgical operation between 1975 and 1978. They were followed‐up until 1987, and a total of 64 deaths including 47 breast‐cancer deaths were certified. The 5‐year and 10‐year relative survival rates were 78.5% and 75.3% respectively. Of the various factors investigated, some anthropometric indicators revealed interesting results; i. e., body weight, Quetelet index, and body surface area at the time of operation turned out to be strong predictors of survival with a statistically significant trend towards lower survival with larger body structure even after adjustment for confounding factors (e. g., clinical stage) using a proportionalhazard model. The estimated survival probability for women with Quetelet index of 20 was about 12% higher than that with Quetelet index of 24 over a 10‐year or more follow‐up period. Other variables exhibiting prognostic importance were clinical stage, TNM classification, and some histological findings, while height and reproductive life indicators were, as a rule, not significantly related to survival.
Quantitation of endogenous lectin expression in 3LL tumors, growing subcutaneously and in the kidneys of mice
Authors: Vidal‐Vanaclocha F. , Barbera‐Guillem E. , Weiss L. , Glaves D. , Gabius H‐J.
Published: February 2007

By means of microdensitometry and image analysis, quantitative measurements were compared of endogenous lectin expression in tissue sections from 3LL carcinomas growing in the subcutis and kidneys of mice following the direct injection of cancer cells. The lectins were visualized by means of a modification of the ABC‐peroxidase technique. In comparison with the subjective, visual inspection of similar materials reported previously, these quantitative techniques not only confirmed, but also provided additional information on siteassociated changes in 3LL cell populations. Previously, 2 classes of cancer cells were recognized within the tumors on the basis of staining intensity, compared with 3 classes in the present study and, in addition, the relative areas occupied by these 3 densitometric classes were determined by imageanalysis. Both “low” and “high” integrated intensities were significantly greater in the kidney tumors in 11 of 24 cases, and in 6 of 24 cases of s. c. tumors. The areas occupied by “high” and “low” intensity cells were significantly higher in 14 of 24 kidney tumors, and in 2 of 24 s. c. tumors. The results indicate often marked differences in endogenous lectin expression, between 3LL cancer cells from a common source, after direct delivery and growth in 2 different anatomic sites. These results indicate the necessity of taking into account analogous changes, when comparing these and other properties of cancer cell populations in metastases with those in primary tumors, with respect to both the generation of siteassociated differences and their possible site‐associated abrogation.
Physical activity and colon cancer: A case‐referent study in Stockholm
Authors: De Verdier Maria Gerhardsson , Steineck Gunnar , Hagman Ulla , Rieger Åke , Norell Staffan E.
Published: February 2007

A population‐based case‐referent study on physical activity (during working and recreational hours) and colon cancer was performed in Stockholm in 1986‐1988. The study included 1,081 subjects. Low physical activity was associated with an excess risk of colon (but not rectum) cancer for both men and women, showing a dose‐response relationship with decreasing levels of physical activity. The effect was seen in the left colon (relative risk = 3.2, 95% confidence interval = 1.5–7.0) rather than in the right colon (relative risk =1.1, 0.5–2.5). These results persisted after adjustment for year of birth, gender, body mass, intake of total energy, protein, total fat, dietary fibre, and browned meat surface.
Type of alcoholic beverage and cancer of the oral cavity, pharynx and oesophagus in an Italian area with high wine consumption
Authors: Barra Salvatore , Franceschi Silvia , Negri Eva , Talamini Renato , La Vecchia Carlo
Published: February 2007

The role of different types of alcoholic beverage on cancer of the upper digestive tract was investigated in a case‐control study conducted in the northern part of Italy on 305 male cases of cancer of the oral cavity and pharynx, 288 of oesophageal cancer and 1621 controls admitted to hospital for acute, non‐neoplastic conditions, unrelated to alcohol intake. Similar significant trends of risk increase with increasing alcohol intake were seen for cancers of the oral cavity, pharynx and oesophagus independent of type (or types) of beverage consumed. Among the heaviest drinkers (i. e. ≥84 drinks/week) odds ratios (ORs) of cancer of the oral cavity and pharynx for wine only, wine and spirits, and combination of wine, spirits, and beer were 11.2, 9.9 and 4.1, respectively. Corresponding oesophageal cancer ORs were 15.0, 10.0 and 6.0. This study from an area with high wine consumption confirms that wine per se can greatly enhance the risk of cancer of the upper digestive tract and suggests that the most frequently used alcoholic beverage in each study appears to be the most important determinant of these tumours.
Expression and modulation by cytokines of the intercellular adhesion molecule‐1 (ICAM‐1) in human central nervous system tumor cell cultures
Authors: Guarini Ludovico , Temponi Massimo , Bruce Jeffrey N. , Bollon Arthur P. , Duigou Gregory J. , Moulton Thomas A. , Ferrone Soldano , Fisher Paul B.
Published: February 2007

The intercellular adhesion molecule (ICAM‐1) has been shown to be important in interactions involying cells of the immune system and to be upregulated in a number of cell culture systems by cytokines, including immune interferon (IFN‐γ) and tumor necrosis factor‐alpha (TNF‐α). In the present study, we have determined by fluorescence‐activated cell sorter (FACS) analysis and the anti‐ICAM‐I monoclonal antibody (MAb) CL203.4 the base‐line expression of ICAM‐I and its modulation by recombinant IFN‐β, IFN‐γ and TNF‐α in early passage (< 15) human central nervous system (CNS) tumor‐derived cell cultures. These cultures were established from various malignancies, including glioblastoma multiforme (GBM), astrocytoma (AST), ganglioglioma, medulloblastoma, meningioma and a pineal tumor. ICAM‐I expression was highest in the GBM‐ and AST‐derived cell cultures and was lowest in the ganglioglioma and normal pineal cell cultures. Variable ICAM‐I expression was found, however, in tumors of the same histological group. In several cell cultures the variable expression observed by FACS was substantiated by the intensity of the molecular species immunoprecipitated by the anti‐ICAM‐I MAb CL203.4 from these cells. All the cell cultures displayed variable but consistent increases in ICAM‐I expression following treatment with IFN‐γ or TNF‐α. In general, the degree of increase in ICAM‐I expression was greatest in cultures exposed to TNF‐α. Upregulation of ICAM‐I expression in an established glioblastoma multiforme cell line was of greater magnitude and more rapid following TNF‐α treatment (within 2 to 3 hr) than exposure to IFN‐γ (by 24 hr). In several cultures, IFN‐β also increased ICAM‐I expression and enhanced the increase induced by TNF‐α. The results of the present study indicate that variable expression of ICAM‐I is a common property of early passage cultures of CNS tumors and recombinant interferons and TNF‐α can differentially upregulate ICAM‐I expression in these CNS tumor cell cultures.
Characterization of a sialic‐acid‐rich mucus glycoprotein secreted by a premalignant human colorectal adenoma cell line
Authors: Corfield Anthony P. , Clamp John R. , Casey Angela D. , Paraskeva Christos
Published: February 2007

The human colonic cell line PC/AA, derived from an adenoma, retains in vitro colonic cell differentiation, notably the production of mucus glycoproteins. The PC/AA adenoma cells produce an extracellular gel layer in culture. The PC/AA gel could be isolated by extraction of the cell cultures with guanidine hydrochloride. The extracted material was purified by gel filtration and caesium chloride density‐gradient centrifugation and showed properties typical of mucus glycoproteins, namely, a carbohydrate content above 60% of dry weight rich in N‐acetylgalactosamine and sialic acid and low in mannose; an amino acid composition with high serine threonine and proline content; a molecular weight above 1,000 kDa on Sepharose CL 4B chromatography and on SDS‐polyacrylamide gel electrophoresis under reducing conditions (>200 kDa); a buoyant density of approximately 1.48 g/ml and the release of oligosaccharides by the alkaline β‐elimination reaction. Comparison of the gel mucus glycoprotein purified from premalignant PC/AA cells with normal human colon much showed that it has a higher sialic acid content. This suggests that higher sialic acid levels may precede the development of malignancy.
Steroid hormone receptor gene expression in human breast cancer cells: Inverse relationship between oestrogen and glucocorticoid receptor messenger RNA levels
Authors: Hall Rosemary E. , Lee Christine S. L. , Alexander Ian E. , Shine John , Clarke Christine L. , Sutherland Robert L.
Published: February 2007

The relative expression in human breast cancer cells of messenger ribonucleic acids (mRNA) encoding different steroid hormone receptors is unknown. Accordingly, mRNA levels in total RNA extracted from 13 human breast cancer cell lines were measured by Northern analysis employing complementary DNA probes for the human oestrogen (ER), progesterone (PR), androgen (AR), vitamin D3 (VDR) and glucocorticoid receptors (GR). The 7 ER+ lines expressed a single 6. 4 kilobases (kb) ER mRNA. Interestingly, low concentrations of ER mRNA were detected in the ER− cell lines, MDA‐MB‐330 and BT 20. PR mRNA, predominaintly a 13.5 kb species, was expressed in the 6 lines known to be ER+, PR+ by radioligand binding; however, one ER+ cell line, MDA‐MB‐134, failed to express PR mRNA. A 10.5 kb AR mRNA was expressed at significantly higher levels in ER+ than ER− cell lines. All cell lines expressed a single 4.6 kb mRNA for VDR and a single 7.4 kb mRNA for GR. ER and PR mRNA levels were positively correlated (p = 0.011) and each was positively correlated with androgen receptor (AR) mRNA levels (p < 0.009). ER, PR and AR mRNAs were negatively associated with GR levels (p < 0.012), while ER and AR mRNA levels were negatively correlated with mRNA for the epidermal growth factor receptor. In contrast, levels of VDR mRNA were unrelated to the concentration of any other steroid receptor mRNA. Our data demonstrate the coordinate expression of ER, PR and AR genes, and an inverse relationship between sex steroid hormone receptor and GR gene expression in human breast cancer cell lines.
Augmentation for intratumoral accumulation and anti‐tumor activity of liposome‐encapsulated adriamycin by tumor necrosis factor‐α in mice
Authors: Suzuki Shinya , Ohta So , Takashio Kazutoshi , Nitanai Hironobu , Hashimoto Yoshiyuki
Published: February 2007

The effect of recombinant human tumor necrosis factor‐α (rhTNF‐α) on anti‐tumor activity of adriamycin entrapped in small unilamellar liposomes (ADM‐Lip) has been studied using BALB/c mice bearing subdermal Meth‐A fibrosarcoma. Accumulation of i. v. injected ADM‐Lip, but not of free ADM, into tumor tissue was augmented by a single i. v. injection of rhTNF‐α. The maximum effect of rhTNF‐α was expressed when it was injected 1 hr before ADM‐Lip. This rhTNF‐α treatment did not result in increased accumulation of ADM‐Lip in normal organs. Based on these results, we treated mice bearing Meth‐A tumor with rhTNF‐α and then with ADM‐Lip 1 hr later. By 2‐cycle treatments using this regimen, tumor growth was markedly inhibited, and 5 out of 13 mice tested were cured of tumor, while treatment with rhTNF‐α alone, ADM alone, ADM‐Lip alone or rhTNF‐α plus ADM resulted neither in prolongation of survival time nor in cure of mice. Our results indicate that ADM‐Lip can express a potent and systemic anti‐tumor activity after pretreatment of animals with TNF, but only when administration of these drugs is appropriately timed.
Type‐II estrogen binding sites in a lymphoblastoid cell line and growth‐inhibitory effect of estrogen, anti‐estrogen and bioflavonoids
Authors: Scambia Giovanni , Ranelletti Franco O. , Panici Pierluigi Benedetti , Piantelli Mauro , Rumi Carlo , Battaglia Francesco , Larocca Luigi M. , Capelli Amaldo , Mancuso Salvatore
Published: February 2007

Type‐II estrogen‐binding sites (type‐II EBS) have been demonstrated in the human lymphoblastoid cell line IM‐9 using a whole‐cell assay with (6, 7‐3H) estradiol (3H‐E2) as tracer. Competition analysis showed that the anti‐estrogen tamoxifen and the flavonoids quercetin and rutin competed for (3H)‐E2 binding to type‐II EBS. Growth experiments demonstrated that diethylstilbestrol (DES) tamoxifen (TAM), quercetin and rutin exerted a reversible dose‐dependent inhibition of cell proliferation in the range of concentrations between 10 nM and 10 μM. The relative binding affinity of quercetin, rutin, DES and TAM for type‐II EBS correlated well with their potency as cell growth inhibitors. Moreover, hesperidin, a flavonoid which does not bind to type‐II EBS, was ineffective in inhibiting cell growth. Cell‐cycle analysis showed that the growth‐inhibitory effect of DES, TAM or quercetin was due to a blocking effect in the G0‐G1 phases. Our results suggest that high estrogen and anti‐estrogen concentrations and flavonoids may regulate IM‐9 cell growth through a common mechanism involving a binding interaction with type‐II EBS.
Nutritional factors and pancreatic cancer in the francophone community in montréal, Canada
Authors: Ghadirian P. , Simard A. , Baillargeon J. , Maisonneuve P. , Boyle P.
Published: February 2007

In a population‐based case‐control study of dietary risk factors for pancreatic cancer, a total of 179 cases and 239 controls were interviewed between 1984 and 1988. This study demonstrated an increased risk of pancreas cancer associated with high levels of reported energy intake. After adjustment for age, sex, response status, lifetime cigarette consumption and energy intake, there appeared to be an association with total fat intake (odds ratio in highest quartile relative to lowest quartile 2.24 [95% Confidence Interval (0.74, 6.73)] and, particularly, saturated fat [OR = 4.32, 95% CI(1.39,13.7)]. Although dietary cholesterol intake appeared to increase risk and a number of many micro‐nutrients were apparently associated with reductions of risk, none were statistically significant. The results are consistent with a role of nutritional factors in the etiology of pancreatic cancer. The magnitude of the risks involved emphasizes the necessity for larger studies of this topic.
The analysis of restriction fragment length polymorphism in human cancer: A review from an epidemiological perspective
Authors: Vineis Paolo , Caporaso Neil
Published: February 2007

We have reviewed published case‐control studies on the role of Restriction Fragment Length Polymorphism (RFLP) for specific loci in the causation of human cancer or as a prognostic factor. Five studies have been published on L‐myc polymorphism and prognosis for several types of cancer (lung, kidney, stomach or breast). Sixteen studies report on Ha‐ras polymorphism and the risk of cancers in the lung, breast, bladder, colorectum, brain, leukemias and melanoma. The results of the studies are conflicting. In addition, such studies raise important methodological issues: the choice of the cut‐off between “rare” and “common” alleles; the inclusion of prevalent cases; the distribution of the alleles in subgroups of the population, including different ethnic groups; a mechanistic interpretation of the role played by the polymorphism, including possible interaction with environmental exposures. These questions need to be answered before a cause‐effect relationship can be clearly established.
Characterization of NCAM expression and function in BT4C and BT4Cn glioma cells
Authors: Andersson A.‐M. , Moran N. , Gaardsvoll H. , Linnemann D. , Bjerkvig R. , Laerum O. D. , Bock E.
Published: February 2007

The neural cell adhesion molecule, NCAM, plays an important role in cell‐cell adhesion. Therefore, we have studied NCAM expression in the glioma cell lines BT4C and BT4Cn. We demonstrate that the 2 cell lines differ in their metastatic ability; while BT4C cells have a very low capacity for producing experimental metastases, that of BT4C cells is high. In BT4C cells NCAM is synthesized as 4 polypeptides with Mr's of 190,000, 140,000, 115,000 and 97,000. The 140,000, 115,000 and 97,000 polypeptides are glycosylated and for the 140,000 and 115,000 polypeptides sulfatation is observed. Conversely, no NCAM protein synthesis is observed in BT4Cn cells, even though NCAM mRNA is expressed. Thus, development of an increased metastatic capacity is accompanied by the disappearance of NCAM protein expression in this model system. The functional importance of NCAM expression was studied by a cell‐substratum binding assay in which the binding of BT4C and BT4Cn cells to NCAM immobilized to glass was assessed. We found that BT4C cells adhere specifically to NCAM, and that adhesion is inhibited by anti‐NCAM Fab'‐fragments, while no specific binding of BT4Cn cells to NCAM was observed. The BT4C and BT4Cn cell lines thus constitute an important new model system for the study of tumor invasion and metastasis and of the role of cell adhesion molecules in these processes.
Regional heterogeneity in breast carcinoma: Thymidine labelling index, steroid hormone receptors, dna ploidy
Authors: Meyer John S. , Wittliff James L.
Published: February 2007

We examined multiple samples of 65 primary breast carcinomas larger than I cm in diameter for thymidine labelling index (TLI), DNA index (DNAI, a measure of cellular DNA content by flow cytometry), and estrogen (ER) and progesterone (PgR) receptors by radioligand‐binding. One or more axillary metastases were also assayed in 11 patients. Two to 15 samples were successfully assayed for TLI from 59 tumors, 2‐31 samples for DNAI from 61 tumors, and 2‐15 samples from 55 tumors for ER and PgR. Criteria for heterogeneity were excess inter‐sample variance in comparison with intra‐sample variance at the p < 0.05 level for TLI and DNAI, and variation of clinically significant magnitude in assay results for ER and PgR. Sixty‐one percent of tumors were heterogeneous for TLI, 26% for DNAI, 24% for ER and 40% for PgR. High TLI disposed toward heterogeneity for TLI itself (p = 0.06), for ER (p = 0.04), and for PgR (p = 0.007). Young age favored heterogeneity for TLI (p = 0.12), ER (p = 0.002), and PgR (p = 0.04). Heterogeneity for DNAI was not related to age and TLI status but was more common in larger tumors (p = 0.08). After consideration of relationships between TLI, age, size, ER and PgR, TLI rather than age appears to be the more important determinant of heterogeneity for receptors. High TLI could lead to heterogeneity through increased numbers of cell divisions that favor emergence of variant stemlines, or by causing local vascular and humoral disparities through rapid growth. Regional heterogeneity can explain erroneous prognostic predictions in approximately 10% to 20% of breast carcinoma patients. We recommend multiple sampling of large breast carcinomas and analysis of axillary metastases for study of tumor markers.
Decreased tumorigenicity of a transplantable rat sarcoma following transfer and expression of an IL‐2 cDNA
Authors: Russell Stephen J. , Eccles Suzanne A. , Flemming Claudia L. , Johnson Caroline A. , Collins Mary K. L.
Published: February 2007

The notion that tumour‐cell‐derived IL‐2 might lead to paracrine stimulation of the host anti‐tumour response was tested in a transplantable rat sarcoma model. Three HSNLV clones induced to secrete different amounts of human IL‐2 following retroviral gene transfer showed reduced tumorige‐nicity and metastatic potential in athymic (nu/nu) and immunocompetent syngeneic rats which was directly related to the level of IL‐2 secretion. In contrast, the tumorigenicity of HSNLV clones secreting a biologically inactive form of IL‐2 (IL‐2Lys20) was unaltered. T‐lymphocyte‐mediated rejection of Zip I, the highest IL‐2 producer, was demonstrated histologically in hooded rats and infiltrating mononuclear cells were also observed in Zip I tumours growing in athymic rats. Tumours derived from IL‐2‐secreting HSNLV showed reduced or absent IL‐2 secretion in immunocompetent rats, sometimes with associated loss of the IL‐2 provirus, but continued to secrete IL‐2 in nude rats. The host response to Moloney‐helper‐virus‐infected HSNLV was also examined and the results represent a cautionary note to those undertaking experiments of a similar nature.
Establishment and characterization of five human malignant mesothelioma cell lines derived from pleural effusions
Authors: Manning Linda S. , Whitaker Darrel , Murch Ashleigh R. , Garlepp Michael J. , Davis Mark R. , Musk Arthur W. , Robinson Bruce W. S.
Published: February 2007

Malignant mesothelioma (MM) is an aggressive tumour of the serosal cavities which is associated with exposure to asbestos. Studies of this tumour have been limited by a paucity of well‐characterized human MM cell lines. In this study, 5 human MM cell lines were established from pleural effusions of patients with this malignancy. All 5 patients were males with known crocidolite asbestos exposure, who had received no treatment for their disease and in whom the diagnosis was confirmed by cytology, histology and electron microscopy (EM). These lines have been in culture from 11 to 25 months, and all of them for more than 18 passages. The appearance of the cells in culture was extremely varied; in 3 of the lines they were spindle‐shaped with few vacuoles (JU77, LO68 and ONE58); in I line they had a thick, stellate shape with vacuoles (NO36) and in I they were very pleomorphic in both shape and size with irregular membranes and numerous vacuoles [DeHI28 (M)]. Upon reaching confluence, cells in 3 of the 5 lines assumed the cobblestone‐like pattern characteristic of epithelial‐type cells, whereas in the other 2 (LO68 and ONE58) they remained spindle‐shaped. All 5 lines demonstrated a loss of contact inhibition (i.e., piling) at confluence. Minimum doubling times varied significantly from 18 hr (JU77) to more than 30 hr [DeHI28 (M)]. Cytological examination showed characteristic mesothelial/mesothelioma morphology, and epithelial membrane antigen (EMA) and cytokeratin were demonstrated in cells from all 5 lines. These cells lacked CEA and epithelial mucin. The presence of cell junctions, glycogen and numerous long, thin, branching microvilli was readily demonstrable by EM. All lines had abnormal karyotypes, with the modal chromosome number varying from 40 to 80. Variable chromosome numbers, numerous structural rearrangements and unrecognizable marker chromosomes were readily observed; however, the only consistent change seen was del 6q2l in 4 of the 5 lines. The establishment of these 5 cultured human MM cell lines now provides an opportunity for comparative study of several aspects of the biology of MM in vitro as well as screening new treatment modalities.
α2, 6 sialylation of N‐acetyllactosaminic sequences in human colorectal cancer cell lines. Relationship with non‐adherent growth
Authors: Dall'olio Fabio , Malagolini Nadia , Stefano Giuseppina Di , Ciambella Manuela , Serafini‐Cessi Franca
Published: February 2007

In a previous work we found that human colorectal cancer tissues express increased levels of an α2,6 sialyltransferase (α2,6 ST) acting on N‐acetyllactosaminic sequences (E.C. 2.4.99.1). In this study we have taken advantage of the known specificity of elderberry bark lectin (Sambucus nigra agglutinin, SNA) for NeuAcα2, 6Gal/GalNAc structures to investigate the relationship between expression of α2,6 sialyltransferase activity and occurrence of α2,6‐sialylated oligosaccharide sequences in human colorectal cancer cell lines. Three cell lines with opposite adhesion properties were used in this study: SW 948 cells grow adherent to the culture flask surface and express very low levels of enzyme activity; COLO 205 cells grow in non‐adherent form and express the highest levels of α2,6 ST activity; A non‐adherent subline of SW 948 cells (SW 948 FL) was isolated and found to express high levels of α2,6 ST activity. By using SNA‐Sepharose chromatography we found that expression of α2,6 ST activity correlates with the extent of α2,6‐sialylation of N‐linked chains of glycoproteins but not with the presence of α2,6‐sialylated glycolipids.
Purification of an autoantigenic 75‐kDa human melanosomal glycoprotein
Authors: Vijayasaradhi Setaluri , Houghton Alan N.
Published: February 2007

Only a few autoantigenic human tumor antigens have been purified and characterized. We employed the monoclonal antibody (MAb) TA99 to isolate, purify and partially characterize an autoantigenic intracellular glycoprotein, gp75, from human melanoma cells. The gp75 antigen is the most abundant glycoprotein expressed in human melanocytes and pigmented melanomas and is the human homologue of the mouse brown locus gene product. Differential solubilization of melanoma membrane fraction and subcellular fractionation of pigmented melanoma cells showed that gp75 is an integral membrane protein localized to melanosomes. The gp75 glycoprotein eluted as a broad peak during ion exchange chromatography and appeared as a protein with broad pl (pl 5.5‐5.9), consistent with charge microheterogeneity. gp75 also exhibited heterogeneity of binding to concanavalin A. Tyrosine hydroxylase (tyrosinase) activity co‐purified with gp75 during membrane solubilization and anion exchange and Con A chromatography. However, most tyrosine hydroxylase activity could be dissociated from gp75 antigen during MAb TA99 affinity chromatography. TA99 did not immunoprecipitate or deplete tyrosine hydroxylase activity from lysates of human melanoma cells. Attempts to obtain N‐terminal amino acid sequence of purified gp75 were not successful due to blocked N‐terminus. Amino acid composition of gp75 was similar to that of tyrosinase. Physicochemical similarities and limited identity in the primary structure between gp75 and tyrosinase support the conclusion that the gp75 antigen does not exhibit tyrosine hydroxylase activity, but is a member of a tyrosinase‐related family of proteins.
Counteracting effects of dexamethasone and α2‐macroglobulin on inhibition of proliferation of normal and neoplastic rat hepatocytes by transforming growth factors‐β type 1 and type 2
Authors: Wollenberg G. K. , Lamarre J. , Semple E. , Farber E. , Gauldie J. , Hayes M. A.
Published: February 2007

Primary cultures of hepatocytes isolated from normal F‐344 rats or from F‐344 rats with hepatocellular carcinomas generated by a 2‐step model of chemical carcinogenesis were used to determine if dexamethasone (DEX) or α2‐macroglob‐ulin (α2M) modify the ability of transforming growth factors‐β type 1 (TGF‐β1) and type 2 (TGF‐β2) to inhibit labelling index of hepatocytes cultured continuously with or without epidermal growth factor (EGF). Both TGF‐β1 and β2 were equivalently potent inhibitors of S‐phase DNA synthesis in normal and neoplastic hepatocytes as determined by 3H‐thymidine autoradiography. Both DEX (1 to 100 μM) and α2M (50‐200 μm) partially counteracted the mito‐inhibitory effect of both TGF‐βs on the proliferation of normal and surrounding hepatocytes. In contrast, neoplastic hepatocytes cultured with DEX released much less immunoreactive α2M and were less able to overcome the inhibitory effect of TGF‐β than normal or surrounding hepatocytes. Purified bovine α2M partially counteracted the inhibition of TGF‐β1 or β2 of both surrounding and neoplastic hepatocytes. Both DEX and α2M were more effective against the mito‐inhibitory activity of TGF‐β2. Our data suggest that α2M released by DEX‐treated normal hepatocytes contributes to the counteraction of the TGF‐β effect by DEX. Our results support the hypothesis that glucocorticoids and growth‐factor‐binding proteins may have important roles in modulating the effects of TGF‐β on normal hepatocyte proliferation and suggest that under some conditions hepatocellular neoplasms can be more sensitive than normal hepatocytes to inhibition of proliferation by TGF‐β.
Histomorphologic and immunophenotypic spectrum of primary gastro‐intestinal B‐Cell lymphomas
Authors: Mielke Birgit , Möller Peter
Published: February 2007

In order to compare primary gastro‐intestinal (GI) B‐cell lymphomas histomorphologically and immunophenotypically with orthologous steps of B‐cell differentiation within the mucosa‐associated lymphoid tissue (MALT) of the GI tract, a comprehensive panel of well characterized leucocyte differentiation antigens was composed. It comprised immunoglobulin constituents CD5, CD10, CD11c, CD20, CD23, CD24, CD30, CDw32, CD38, CD39, CDw75, CD76, and vimentin. These antigens yield characteristic immunoprofiles for the following B‐cell compartments of the MALT, per se closely linked to cytologically distinct B‐cell phenotypes: mantle zone (MZ), extrafollicular compartment (EF), follicle center (FC), and plasma‐cell compartment (PC). An unselected series of 31 MALT B lymphomas (13 of low and 18 of high grade malignancy) was classified histologically in routine preparations and subsequently characterized immunohistochemically using fresh frozen tissue, monoclonal antibodies (MAbs) against the antigen panel listed above, and an indirect immunoperoxidase method. The final classification considered both morphology and immunoprofile of tumor cells. Ten tumors were “typical” in both respects: 2 closely corresponded to MZ, 5 to EF, 2 to FC and 1 to PC. The remaining 21 cases were characterized as “atypical” because of anaplastic cytology and/or abnormal co‐expression and/or loss of antigens. A hybrid EF/FC phenotype was most frequently observed together with centrocyte‐like or centrocytic anaplastic cytology of tumor cells. We conclude that MALT B‐cell neoplasia comprises a broad spectrum of histo‐ and immunophenotypes ranging from well differentiated forms closely mimicking normal B‐cell development to highly abnormal tumors which cannot be subclassified.
Socio‐economic indicators, infectious diseases and hodgkin's disease
Authors: Serraino Diego , Franceschi Silvia , Talamini Renato , Barra Salvatore , Negri Eva , Carbone Antonino , La Vecchia Carlo
Published: February 2007

The relationship between socio‐economic indicators, family size, history of tonsillectomy, infectious mononucleosis (IM) and other diseases and the risk of Hodgkin's disease (HD) was investigated in a hospital‐based case‐control study, conducted in the province of Pordenone, North‐east Italy, between June, 1985 and March, 1990. One hundred and fifty‐two HD cases (88 men and 64 women) and 613 controls (357 men and 256 women) were interviewed. Patients with 14 or more years of education had a 2‐fold increased HD risk (95% confidence interval, CI: 1.0‐3.9); such risk tended to be higher in patients with nodular sclerosis (NS) HD (odds ratio, OR: 4.4, 95% CI 1.8‐11.0). Sibship size, birth order and tonsillectomy were not associated with HD risk. Cases and controls did not differ in the frequency or age at occurrence of common childhood infections. A history of IM, however, was found to be an important predictor of HD risk, in particular among NS HD (OR = 13.1, 95% CI 1.0‐176.7). Past episodes of herpes zoster and of skin and genital warts were also associated with significantly increased HD risks. These data lend further support to the role of the IM agent (i.e., the Epstein‐Barr virus) and, perhaps, of other viral infections and immunological alterations in the development of HD.
Production of fibronectin by human tumor cells and interaction with exogenous fibronectin: Comparison of cell lines obtained from colon adenocarcinomas and squamous carcinomas of the upper aerodigestive tract
Authors: Varani James , Schuger Lucia , Fugiel Suzanne E. G. , Inman Dennis R. , Chakrabarty Subhas
Published: February 2007

Cell lines derived from 13 different human colon adenocarcinomas were examined for production of fibronectin by ELISA and for cell‐surface expression of fibronectin by indirect immunofluorescence. Two squamous epithelial cell lines obtained from tumors of the upper aerodigestive tract were used as controls. None of the 13 colon carcinoma lines produced detectable amounts of fibronectin or showed detectable cell‐surface staining with anti‐fibronectin. The 2 squamous epithelial cell lines, in contrast, produced large amounts of fibronectin which could be detected in the culture medium and bound to the substratum. The squamous carcinoma cells also stained brightly when examined in the viable state by immunofluorescence with anti‐fibronectin. In addition to being studied for fibronectin production, each cell line was also examined for the ability to interact with exogenous fibronectin in an adhesion assay. None of the colon carcinoma cells were adherent to fibronectin‐coated culture dishes while the 2 squamous carcinoma cells rapidly attached and spread on this substratum. These data suggest that cell lines derived from adenocarcinomas of the colon are deficient in production of fibronectin and in their ability to interact with exogenous fibronectin. In their degree of deficiency, the colon carcinoma cells are significantly different from several different types of human tumor cell. The failure of the colon carcinoma cells to synthesize detectable amounts of fibronectin endogenously or to interact with exogenous fibronectin may explain, in part, the low degree of adhesive interaction which these cells have for their substratum. This, in turn, may influence the in vitro and in vivo properties of colon carcinoma cells.
Sequence variations in ltr and env regions of HTLV‐I do not discriminate between the virus from patients with HTLV‐I‐associated myelopathy and adult T‐cell leukemia
Authors: Kinoshita Tomohiro , Tsujimoto Atsumi , Shimotohno Kunitada
Published: February 2007

For detailed comparison of human T‐cell leukemia virus type I (HTLV‐I) in adult T‐cell leukemia (ATL) and HTLV‐I‐associated myelopathy (HAM), the nucleotide sequences of parts of the long terminal repeat (LTR) and env regions of the HTLV‐I proviruses from 12 patients with HAM, 8 patients with ATL and one with both diseases were analyzed. About 340 bp of the LTR U3 region, about 4S0 bp of the 5′ region and about 280 bp of the 3′ region of env were sequenced directly in DNAs amplified by the polymerase chain reaction (PCR) with 2 or 3 sets of primers for each region. Nucleotide insertions, deletions or point mutations were observed at 50 positions in these regions of about 1,000 nucleotides length. None of these changes was specific to either HAM or ATL, and some changes were observed in proviruses from both cases of HAM and ATL. Moreover, the sequences of proviruses isolated from pairs of cell lines established from cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMCs) of the 4 patients with HAM also had different sequences. These results indicate that the proviruses from HAM and ATL are indistinguishable in these sequenced regions, suggesting that these 2 diseases are caused by infection with genetically indistinguishable HTLV‐I. Therefore, the reason why these two distinct diseases, HAM and ATL, develop in HTLV‐I carriers may be based on a host factor(s) or some other factor(s) rather than variation in the virus itself.
Altered dosage of the sex chromosomes in human testicular cancer: A molecular genetic study
Authors: Peltomäki PÄIvi , Lothe Ragnhild , Børresen Anne‐Lise , Fosså Sophie D. , Brøgger Anton , De La Chapelle Albert
Published: February 2007

Thirty‐one males with testicular germ‐cell tumors were studied by Southern hybridization using X‐ and Y‐chromosome‐specific probes as well as a pseudoautosomal probe. Densitometric analysis showed changes in the relative dosage of Y‐chromosomal fragments in tumor DNA from 12 out of 31 patients (39%) as compared to normal DNA from the same patients. In 11 tumors the relative intensity ratios of Y‐chromosome‐specific fragments had decreased from the normal value of I to values between 0 and 0.77. An increase in the Y‐chromosomal dosage was observed in I case. The entire Y chromosome was apparently involved in most patients but 2 tumors revealed regional variation. Tumor DNA of 2 patients with Y‐chromosomal deficiency showed a concomitant increase in the X chromosomal dosage. The pseudoautosomal region that is shared by both sex chromosomes was involved in a total of 8 tumors (26%), 2 of which did not show any obvious dosage changes with probes detecting strictly X‐ or Y‐chromosome‐specific fragments. Autosomal alterations in the present tumor series have been described. A dosage change involving the sex chromosomes accompanied loss of heterozygosity at loci in 3p or lip in 10 tumors out of 15 (67%). Seminomas tended to be affected more often than non‐seminomas by either type of alteration. Our results indicate that changes in the sex chromosomes occur in a substantial proportion of male germ‐cell tumors and, together with other defects, may constitute an important step in tumor development and/or progression.
Increased susceptibility of ifn‐γ‐treated neuroblastoma cells to lysis by lymphokine‐activated killer cells: Participation of ICAM‐1 induction on target cells
Authors: Naganuma Hirofumi , Kiessling Rolf , Patarroyo Manuel , Hansson Mona , Handgretinger Rupert , Grönberg Alvar
Published: February 2007

We have investigated the effect of interferon‐gamma (IFN‐γ) treatment of neuroblastoma cells on the susceptibility to lysis by lymphokine‐activated killer (LAK) cells and examined the participation of cell‐adhesion molecules on the target cells in LAK cell lysis. Untreated neuroblastoma cells expressed lymphocyte‐function‐associated antigen 3 (LFA‐3) and neural‐cell‐adhesion molecule (NCAM), but did not express MHC‐class‐I, MHC‐class‐II, or intercellular‐adhesion molecule 1 (ICAM‐1). IFN‐γ treatment of neuroblastoma cells induced the expression of MHC‐class‐I and ICAM‐1 antigens, but did not affect the expression of MHC‐class‐II, LFA‐3, and NCAM. This was accompanied by an increased susceptibility to lysis by LAK cells. Anti‐ICAM‐1 antibody inhibited partially the increased sensitivity of IFN‐γ‐treated neuroblastoma cells to LAK cell lysis, and blocked completely the increase in binding of LAK cells observed after IFN‐γ treatment of the target cells. These results suggest that the increased LAK sensitivity of IFN‐γ‐treated neuroblastoma cells is partially attributable to the induction of ICAM‐1 on neuroblastoma cells and indicate that post‐binding events also play a role in the increased sensitivity to LAK cell lysis observed after IFN‐γ treatment.
The role of the peyer's patch in the carcinogenesis of lymphoid cells
Authors: Garrett Lenora R. , Byers Paul , Cuchens Marvin A.
Published: February 2007

The dose response to 3‐methylcholanthrene (3‐MC), the promoter effects of 2,6,10,14‐tetramethylpentadecane (pristane) and the target‐organ specificity in the preferential induction of B‐lymphoid malignancies versus thymic tumors were examined. Lymphoid malignancies were induced in approximately 30% of the Copenhagen rats treated with injections in Peyer's patches (PP) of low, intermediate or high doses of 3‐MC. A low dose of 3‐MC induced B‐lymphocytic leukemias or B lymphomas, whereas thymic tumors were detected in rats treated with high doses. Co‐treatment of rats with pristane and 3‐MC resulted in increased incidences and decreased latency of the lymphoid malignancies observed, suggesting that pristane acts as a tumor promoter. To address the possible role of PP in the induction events, PP were surgically removed after 3‐MC treatment and the remaining small intestine anastomosed. Thymic tumors, but no B‐lymphoid malignancies, were observed, indicating that the PP environment was important in the induction of the B‐lymphoid malignancies. Radiotracer studies also revealed that appreciable amounts of 3‐MC were disseminated to the thymus within 24 hr after treatment of PP with a high dose of 3‐MC. Furthermore, direct intrathymic injection of the thymus with 3‐MC resulted in the development of thymic tumors only. These results support the hypothesis that the PP has an important role in early events in the carcinogenesis of B lymphocytes and in the dissemination of 3‐MC to the thymus.
The effect of radiosensitizers on radio‐immunotherapy, using 131I‐Labelled anti‐cea antibodies in a human colonic xenograft model
Authors: Barbara Pedley R. , Begent Richard H. J. , Boden Joan A. , Boden Robert , Adam Theresa , Bagshawe Kenneth D.
Published: February 2007

Anti‐CEA antibodies were used for radio‐immunotherapy in an established LSI74T colonic xenograft in nude mice. A single IV dose of either l3lI‐PK4S (polyclonal) or ‐A5B7 (monoclonal) antibody produced tumour regression, and significantly delayed subsequent tumour growth. Administration of a clearing second antibody, 24 hr post 1311‐PK4S and at 5 times the dose, significantly reduced the therapeutic effect of radio‐antibody alone. Tumours of mice given non‐specific antibody or unlabelled anti‐CEA antibody grew like those of untreated controls. In an attempt to enhance therapy without increasing dose, radiosensitizers normally employed with external beam radiation were used in combination therapy. When the hypoxic cell radiosensitizer misonidazole was combined with 1311‐A5B7, it significantly prolonged tumour‐growth inhibition over radio‐antibody alone. Conversely, the therapeutic effect of either radio‐antibody was significantly reduced when used in combination with the halogenated pyrimidine radiosensitizer 5‐iododeoxyuridine. Neither sensitizer alone affected tumour growth.
Activation of ras oncogenes and expression of tumor‐specific transplantation antigens in methylcholanthrene‐induced murine fibrosarcomas
Authors: Carbone Giusi , Borrello Maria Grazia , Molla Alessandra , Rizzetti Maria Grazia , Pierotti Marco A. , Porta Giuseppe Della , Parmiani Giorgio
Published: February 2007

The DNA of 22 fibrosarcomas, newly induced in BALB/c mice by subcutaneous doses of 3‐methylcholanthrene (3‐MCA), was tested in NIH 3T3 transformation assay. Activation of K‐ras and N‐ras was found in 7 and 3 cases respectively. No H‐ras activation was detected. Polymerase chain reaction and oligonucleotide hybridization performed on the DNA of the 22 sarcomas revealed 5 cases of K‐ras mutation at codon 12, 3 at codon 13 and I at both codons. One case of K13 mutation was not detectable by transfection. Three cases of mutation at codon 61 of N‐ras were also found, one of which was simultaneous with a K12 mutation. Tumor‐specific transplantation antigens (TSTA) were assessed in the 22 original tumors. Altogether 16 sarcomas were immunogenic, with the highest frequency of TSTA tumors (10/11 and 5/6) in the groups given 1.0 and 0.1 mg of 3‐MCA respectively, the lowest (1/5) in that with 0.01 mg of carcinogen; ras mutations occurred in the DNAs of 11 out of the 16 TSTA+ sarcomas, but none of the DNAs of the 6 TSTA‐ tumors showed ras mutation. The results suggest that 3‐MCA‐induced transformation of subcutaneous fibroblasts can involve mutations in codons 12, 13 or 61 of K‐ and N‐ but not H‐ras gene and that such mutation is accompanied by the expression of TSTA.
Involvement of ornithine decarboxylase in the control of proliferation of the HT29 human colon cancer cell line. effect of vasoactive intestinal peptide on enzyme activity
Authors: Gamet Laurence , Cazenave Yolande , Trocheris Véronique , Denis‐Pouxviel Colette , Murat Jean‐Claude
Published: February 2007

Involvement of ornithine decarboxylase (ODC) in proliferation of the HT29 cell line and its control by either fetal calf serum (FCS) or vasoactive intestinal peptide (VIP) as an external signal increasing cAMP level were investigated. Activation of the polyamine‐producing system appears to be a necessary step in the proliferative response of HT29 cells since cell growth is arrested by addition of difluoromethylornithine (DFMO, an inhibitor of ODC), then restored by further addition of putrescine into the culture medium. FCS deprivation results in decreased activity of ODC and arrest of cell growth. Addition of FCS induces reactivation of ODC peaking at 9 hr and re‐initiates proliferation but does not affect cAMP level. VIP strongly and rapidly stimulated cAMP accumulation, which resulted in significant activation of ODC. When VIP‐induced cAMP formation was hindered by the alpha2‐adrenergic agonist UK 14304, activation of ODC was no longer observed. The dose‐response curve for ODC activation by VIP indicates an EC50 value of 0.078 nm which falls within the range of physiological concentrations for this peptide. However, VIP fails to stimulate proliferation when cells are cultured either in an FCS‐free medium or in the presence of a growth‐limiting concentration of FCS. We conclude that the mechanisms of ODC activation by either FCS or VIP are different, the latter involving cAMP formation. Activation of ODC to produce polyamines is necessary to support the proliferative process in our model but the VIP‐induced activation of the enzyme alone is not sufficient to promote cell growth.
Presence of circulating anti‐c‐myb oncogene product antibodies in human sera
Authors: Sorokine Irène , Ben‐Mahrez Kamel , Bracone Annie , Thierry Dominique , Ishii Shunsuke , Imamoto Fumio , Kohiyama Masamichi
Published: February 2007

Bacterially expressed mouse c‐myb protein was purified from E. coli extracts and used as antigen to screen human sera for circulating anti‐c‐myb oncogene product antibodies. Using Western blotting, we have found that human sera contain IgG antibodies to the c‐myb gene product. The percentage of positive sera in cancer patients appears to be dependent upon cancer type and is significantly higher in breast‐cancer patients than in normal donors: 43% of sera from breast‐cancer patients are positive, whereas in neuroblastoma cancer patients the production of IgG anti‐c‐myb appears to be rare. No significant correlation was observed between the presence of circulating anti‐c‐myb antibodies and the expression of the c‐myb gene in breast tumors.
Increasing incidence of cancers associated with the human immunodeficiency virus epidemic
Authors: Rabkin Charles S. , Biggar Robert J. , Horm John W.
Published: February 2007

We examined data from San Francisco and other areas participating in the Surveillance, Epidemiology, and End Results (SEER) Program to determine the effect of the human immunodeficiency virus (HIV) epidemic on cancer incidence between 1973 and 1987. In this period, non‐Hodgkin's lymphoma incidence has increased over 10‐fold and Kaposi's sarcoma incidence has increased over 5000‐fold in single San Francisco men 20 to 49 years of age. Increases in non‐Hodgkin's lymphoma have been restricted to high‐grade and diffuse large‐cell (intermediate‐grade) histological types. With the exceptions of non‐Hodgkin's lymphoma and Kaposi's sarcoma, no other tumor has significantly increased in incidence. During 1987, we estimate that HIV‐seropositive men in San Francisco had a 0.47% risk of developing non‐Hodgkin's lymphoma and a 1.6% risk of developing Kaposi's sarcoma. The relative risks for non‐Hodgkin's lymphoma and Kaposi's sarcoma associated with HIV infection were 104 and 40,000, respectively. For 1987, HIV was associated with 14% of all reported cancers (except non‐melanoma skin cancer) in men aged 20 to 49. We expect that 1,890 to 2,730 excess cases of non‐Hodgkin's lymphoma and 6,490 to 8,320 excess cases of Kaposi's sarcoma will occur in the United States in 1990.