bluuebunny/crossref_metadata_2025 huggingface dataset:
Mucin synthesis and secretion in relation to spontaneous differentiation of colon cancer cells in vitro
Authors: Niv Yaron , Byrd James C. , Ho Samuel B. , Dahiya Rajvir , Kim Young S.
Published: February 2007

The synthesis and secretion of mucin‐like high‐molecular glycoprotein was studied in 2 human colon cancer cell lines that spontaneously differentiate in culture (Caco‐2 and T84) and in 2 cell lines that do not spontaneously differentiate (LS174T and HT29). Mucin, quantitated by 3H‐glucosamine labelling and chromatography on Sepharose CL‐4B was found to be produced by all 4 cell lines. The mucinous nature of the labelled high‐molecular glycoprotein was verified by enzymatic degradation treatments (heparinase, hyaluronidase, chondroitinase ABC, and N‐glycanase), alkaline‐borohydride treatment, inhibition of labelling by the glycosylation inhibitor benzyl‐α‐GaINAc, and by CsCl‐density‐gradient centrifugation. In all 4 cell lines, an inverse correlation of mucin synthesis with cell density was demonstrated. In Caco‐2 cells, the spontaneous post‐confluent enterocytic differentiation with increased brush‐border enzyme expression was associated with a decrease in mucin synthesis and in the activities of polypeptidyl GaINAc transferase and β 1,3‐galactosyltransferase activity. Using cDNA probes for 2 distinct human intestinal mucins (MUC2 and MUC3), we found that all 4 colon cancer cell lines expressed mucin message, but the types of mucin mRNA expressed differed. These data indicate that mucin‐like glycoproteins can be synthesized by cell lines derived from non‐mucinous colon cancer, whether or not they undergo spontaneous differentiation in culture. These cell lines may serve as in vitro models for studying apomucin heterogeneity and control of mucin gene expression.
Characterization of A U‐937 subline which can be induced to differentiate in serum‐free medium
Authors: Öberg Fredrik , Hult Nina , Bjare Ulf , Ivhed Irene , Kivi Sirje , Bergh Jonas , Larsson Lars‐Gunnar , Sundström Christer , Nilsson Kenneth
Published: February 2007

We report the selection and characterization of a U‐937 subline which is capable of long‐term growth in serum‐free medium and can be induced to differentiate. The subline (U‐937‐ISF) can be maintained in standard RPMI‐1640 medium supplemented by antibiotics only. As compared to the serum‐dependent U‐937 parental cell line, U‐937‐ISF produced lower amounts of lysozyme and elastase and had a decreased surface expression of complement receptor I (CD35) and myeloid antigens CDw17 and CD38. Apart from these alterations, the U‐937‐ISF cells appear to be morphologically, cytogenetically and phenotypically similar to the parental U‐937 clone‐1 cells. The capacity of U‐937 clone‐1 cells to undergo phorbol myristic acid (PMA)‐, vitamin D3 (VitD3)‐ and retinoic‐acid (RA)‐induced differentiation was retained in the U‐937‐ISF cells as evidenced by the induced growth arrest, development of a monocyte/macrophage morphology and increased expression of differentiation‐associated antigens, e.g. CD11b, CD11c, CD14 and CD18. The growth‐inhibitory response to cytokines involved in the activation and differentiation of monocytes, IFN‐γ, TNF‐α, IL‐1β, IL‐6 and GM‐CSF, was normal. Our results suggest that the U‐937‐ISF subline can be used as a serum‐free model system for studies on various aspects of monocyte differentiation.
HTLV‐I‐positive and HTLV‐I‐negative peripheral T‐cell lymphomas in Taiwan Chinese
Authors: Shih Lee‐Yung , Kuo Tseng‐Long , Dunn Po , Liaw Shiumn‐Jen
Published: February 2007

The clinico‐pathologic features of 107 adult Chinese patients with peripheral T‐cell lymphoma (excluding primary cutaneous lymphoma) are described and a comparison between HTLV‐I+ and HTLV‐I−patients is made. There were 27 HTLV‐I+ and 80 HTLV‐I−patients. The virus‐positive and‐negative groups both had a male predominance and an identical median age of 48. Most patients in both groups presented with stage‐IV disease, B symptoms, lymphadenopathy and hepatosplenomegaly. The HTLV‐I+ group had a significantly higher incidence of skin and pulmonary lesions, bone marrow and peripheral blood involvement, hypercalcemia, and elevated LDH level compared to the HTLV‐I−group. Sinonasal lesions (10), mediastinal mass (5), and GI tract involvement (6) were only seen in the HTLV‐I−group. Leukocytosis with the presence of circulating pleomorphic lymphoid cells was characteristic of HTLV‐I+ cases, while cytopenia was more frequently present in HTLV‐I−cases. All of the 24 HTLV‐I+ patients tested were CD4+CD8−; of the 67 HTLV‐I−patients tested, 46 were CD4+CD8−, 9 were CD4−CD8+, 5 were CD4−CD8−and 7 were CD4+CD8+. Phenotypic studies revealed significant differences in the expression of CD7 and CD25 between virus‐positive and‐negative groups. Both groups responded poorly to therapy. The median survival of HTLV‐I+ and HTLV‐I−patients was 4 months and 13.5 months, respectively. Apart from the presence of more than 3 extranodal lesions, none of the other clinical features or histologic subtypes had prognostic significance in the entire group or either of the subgroups. This series of peripheral T‐cell lymphomas in Taiwan indicate that HTLV‐I+ and HTLV‐I−patients had many features in common, but presented several distinct differences.
Analysis of regulation of T‐cell responses by soluble inhibitory factors from the sera of patients with Hodgkin's disease
Authors: Damle R. N. , Advani S. H. , Gangal S. G.
Published: February 2007

Soluble inhibitory factors (SIF) have been demonstrated in the sera of cancer patients, which interfere with the T‐cell activation process. We have shown that the major contributory factor to the inhibitory effect of sera from patients with Hodgkin's disease (HD) could be the soluble form of Interleu‐kin‐2 receptors (slL‐2R). The parameters studied to show the presence of SIF include (i) inhibition of mitogen‐induced proliferation; (ii) status of high‐and low‐affinity IL‐2R; and (iii) internalization of IL‐2‐IL‐2R complex, by lymphocytes from healthy donors activated with mitogen in presence of HD sera. Parameters studied to show the inhibitory role of slL‐2R include (i) quantitation of sIL‐2R in HD sera; (ii) effect of high‐sIL‐2R‐containing sera on mitogen‐induced proliferation and detection of IL‐2 in activated lymphocyte culture supernatants; (iii) effect of exogenous IL‐2 supplementation; and (iv) abrogation of inhibitory activity of sIL‐2R‐containing sera after passing them through IL‐2 affinity columns. Our results show that 6/23 HD sera tested had high inhibitory activity (>50% inhibition of mitogen‐induced proliferation). The SIF did not affect expression of high‐and low‐affinity IL‐2 receptors, or internalization of the complex by activated lymphocytes. Ten of the 15 sera tested showed significantly high levels of sIL‐2R. Pooled sera with high sIL‐2R content inhibited mitogen‐induced proliferation of normal lymphocytes with a concomitant reduction in IL‐2 activity in the lymphocyte culture supernatants. When supplemented with exogenous IL‐2, there was a partial recovery of the inhibitory effect. When sIL‐2R containing serum pool was passed on IL‐2 affinity columns, the inhibitory effect was reduced. The eluted “sIL‐2R” adsorbed on the IL‐2 column showed anti‐proliferative effect.
A novel O‐acetylated ganglioside detected by anti‐GD2 monoclonal antibodies
Authors: Ye Jian Nan , Cheung Nai‐Kong V.
Published: February 2007

Murine monoclonal antibody (MAb) 3F8 was previously shown to react with disialoganglioside GD2, but not with GD3, GTIb, GDIb, GDIA,' GMI, GM3 and GM4. However, when the base‐treatment step was omitted from the standard neuroblastoma ganglioside extraction procedure, immuno‐thin‐layer‐chromatography (ITLC) using 3F8 and other anti‐GD2 MAbs revealed a new ganglioside band, abbreviated as NG (Rf 0.342) besides GD2 (Rf 0.183). It migrated below GD3 (Rf 0.358) on high‐performance (HP) TLC plate and its binding to 3F8 on ITLC could be inhibited by rat anti‐3F8 idiotypic antibody Idio‐2, while the binding of GD2 to MAb 3F8 was not affected. Immunochemical analysis showed that this new neuroblastoma ganglioside contained alkali‐sensitive O‐acetylated sialic‐acid residues recognized by MAb DI.I. After base treatment, its subsequent identity on ITLC was confirmed to be GD2. Lactonization of GD2 yielded 2 major bands, with Rf values (0.401, 0.583) distinct from that of the new ganglioside band. In addition, MAb DI. I did not bind to any of these GD2 lactones. Of 15 anti‐GD2 MAbs studied, 13 reacted strongly with the novel ganglioside NG. By ITLC, this NG was found in ganglioside extracts of fresh surgical tumor specimens (4/4 neuroblastomas, I/I schwannoma and I/I anaplastic astrocytoma), and nude mice/rat xenografts (2/2 neuroblastomas, 2/2 osteogenic sarcomas). These data provided the first evidence that O‐acetylated GD2 is a naturally occurring ganglioside derivative in human tumors and that it could cross‐react with most anti‐GD2 antibodies.
Expression of insulin‐like growth factors I and II and their receptor mRNAs in primary human astrocytomas and meningiomas; in vivo studies using in situ hybridization and immunocytochemistry
Authors: Antoniades Harry N. , Galanopoulos Theofanis , Neville‐Golden Janine , Maxwell Marius
Published: February 2007

These studies demonstrate the expression of IGF‐I, IGF‐II, and their respective receptor mRNAs in primary human astrocytomas and meningiomas. In situ hybridization and immunocy‐tochemistry have localized a strong expression of both IGF‐I and IGF‐II mRNAs and of their protein products in the tumor cells of astrocytomas and meningiomas. The expression of IGF‐I and IGF‐II mRNAs in the tumor cells was accompanied by the co‐expression of their respective type‐I and type‐II IGF receptor mRNAs. Control, non‐malignant human brain expressed IGF‐I mRNA and IGF‐I and IGF‐II receptor mRNAs. There was no significant expression of IGF‐II mRNA in the control brain specimens. Control pachymeninges (dura mater) expressed low levels of IGF‐I mRNA and IGF‐I receptor mRNA. There was no significant expression of IGF‐II and IGF‐II receptor mRNAs in pachymeninges. The co‐expression of IGFs and their receptors in brain tumors may contribute in their development and maintenance. The strong inappropriate expression of IGF‐II mRNA and its protein product in the tumor cells of astrocytomas and meningiomas, but not in normal brain specimens, may serve as molecular markers for the early detection of these tumors.
Food consumption and cancer of the colon and rectum in north‐eastern Italy
Authors: Bidoli Ettore , Franceschi Silvia , Talamini Renato , Barra Salvatore , La Vecchia Carlo
Published: February 2007

The relation between dietary factors and the risk of colorectal cancer was investigated in a case‐control study conducted in Pordenone province, North‐eastern Italy, on 123 cases of colon cancer, 125 of rectal cancer and 699 controls admitted to hospital for acute, non‐neoplastic or digestive disorders. Consistent positive associations were observed with more frequent consumption of bread (odds ratio, OR = 2.1 for colon and 2.2 for rectum for highest vs. lowest tertile), polenta (OR = 2.1 for colon, 1.9 for rectum), cheese (OR = 1.7 for colon, 1.8 for rectum) and eggs (2.5 for colon, 1.9 for rectum), whereas reduced ORs were observed in subjects reporting more frequent consumption of tomatoes (OR = 0.5 for colon and 0.4 for rectum). High consumption of margarine exerted a significant protection against cancer of the colon whereas high consumption of carrots, spinach, whole‐grain bread and pasta (favorably) and red meat (unfavorably) affected rectal cancer risk in particular. Thus the present study gives support for a protective effect associated with a fiber‐rich or vegetable‐rich diet, while it indicates that frequent consumption of refined starchy foods, eggs and fat‐rich foods such as cheese and red meat is a risk factpr for colo‐rectal cancer.
Elevated p53 RNA expression correlates with incomplete osteogenic differentiation of radiation‐induced murine osteosarcomas
Authors: Strauss P. Günter , Mitreiter Karin , Zitzelsberger Horst , Luz Arne , Schmidt Jörg , Erfle Volker , Höfler Heinz
Published: February 2007

An important role for the p53 gene in osteogenic sarcomas has been imputed by identification of somatically acquired gene alterations in human osteosarcomas and by the development of osteosarcomas in p53 transgenic mice. To study the involvement of p53 in radiation‐induced osteosarcomagenesis, we have investigated gene alterations and expression of p53 in radiationinduced murine osteosarcomas and tumor‐derived cell lines. Eighteen of 31 tumors and 8 of 9 cell lines showed alterations in the p53 gene region, or elevated levels of p53 RNA. Expression of the osteoblast marker gene bone gla protein was substantially reduced in tumors which simultaneously showed high steady‐state levels of p53 RNA. Our data indicate that p53, in addition to its function in regulating DNA synthesis, may be involved in the control of osteogenic differentiation in osteosarcomagenesis.
Local growth of a Burkitt's lymphoma versus disseminated invasive growth of the autologous EBV‐immortalized lymphoblastoid cells and their somatic cell hybrids in SCID mice
Authors: Walter Jürgen , Möller Peter , Moldenhauer Gerhard , Schirrmacher Volker , Pawlita Michael , Wolf Jürgen
Published: February 2007

Specific host‐graft interactions, as well as intrinsic properties of transferred cells, determine tumorigenicity in xenogeneic systems. We compared the growth characteristics of human B‐lymphoid cell lines in SCID mice with the well characterized growth pattern in nude mice and observed striking differences in malignancy in the respective hosts. Two cell lines derived from the same individual, the Epstein‐Barr‐virus(EBV)‐positive Burkitt's lymphoma BL 60 (BL) and the auto logouts EBV‐immortalized lymphoblastoid cell line IARC 277 (LCL) were used. In addition, we tested somatic cell hybrids (HYB) of both cell lines, which despite the LCL‐like differentiation phenotype show the de‐regulated c‐myc expression pattern of the parental BL line, assumed to be a critical factor in BL pathogenesis. Subcutaneously (s.c.) injected BL cells produced local progressively growing tumor masses at the injection site without distant metastases in both nude and SCID mice. Although both mouse strains possess the same genetic background (BALB/c) and differ only in the B‐cell sub‐set, the growth patterns of the LCL and hybrids were completely different. In contrast to the regressive behaviour of LCL and hybrids in nude mice, these lines show invasive and disseminated progressive growth in SCID mice. Peripheral lymph nodes and thymes tissue were preferentially colonized, whereas mucosal‐associated lymphoid tissue (Peyer's patches and appendix) and spleen were not infiltrated. The preferential migration of lymphocytes to certain tissues is termed homing in a gynogenic system and mediated by homing receptors and vascular addressing. The “homing” of LCL and hybrids into lymphoid SCID mouse tissue suggests a strong interaction with the endothelial cells of the host. Detailed phenotypic analysis of BL, LCL and 3 different hybrids was performed using an antibody panel against differentiation and adhesion markers. Overall dominance of the LCL phenotype was observed in the hybrids, as indicated by cytology, tumor growth, dissemination and the pattern of surface‐marker expression. The c‐myc activation in hybrids does not appear to influence growth behavior.
Growth‐factor‐independence and invasive properties of colorectal carcinoma cells
Authors: Williams Noel N. , Györfi Tibor , Iliopoulos Dimitrios , Herlyn Dorothee , Greenstein David , Linnenbach Alban J. , Daly John M. , Jensen Pamela , Rodeck Ulrich , Herlyn Meenhard
Published: February 2007

During serial passage of the colorectal carcinoma cell line SW1116 in athymic nude mice, we selected 2 variants that metastasized to the lungs and liver. The metastatic capacity of these in vivo variant cell lines was associated with their ability to (1) grow under growth‐factor‐deprived conditions, (2) invade and transgress a reconstructed basement membrane with high effectiveness, and (3) produce higher activities of the substrate‐ degrading enzymes collagenase and plasminogen activator as compared to parental cells. To assess the relative contribution of growth‐factor‐independence and high levels of invasiveness/motility to the metastatic phenotype, variants of 6 colorectal carcinomas were selected in vitro by adaptation to a growth‐factor‐free culture medium followed by selection of highly invasive cells in chemoinvasion assays. Four out of 6 cell lines selected for growth‐factor‐independence showed significantly higher levels of invasiveness through reconstructed membranes, suggesting co‐segregation of growth‐factor‐independence and high levels of invasiveness in vitro. Using an in vitro chemoinvasion assay, 2 poorly and I highly invasive cell line were further selected for invasiveness. After 6 selection passages, all cell lines were highly invasive and showed high motility rates. However, when injected s.c. into athymic nude mice to test their metastatic capacity in vivo, double‐selected variant cell lines did not form spontaneous metastases. Our results indicate that growth‐factor‐independence and high levels of invasiveness, although associated with the metastatic phenotype, are not sufficient for experimental metastasis formation of colorectal carcinoma cells in vivo.
Inhibition of azoxymethane‐induced experimental colon carcinogenesis in wistar rats by 6‐hydroxydopamine
Authors: Tatsuta Masaharu , Iishi Hiroyasu , Baba Miyako , Taniguchi Haruo
Published: February 2007

The effects of 6‐hydroxydopamine (6‐OHDA) on the incidence, number and histology of colon tumors induced by azoxymethane (AOM), and on norepinephrine (NE) concentration in the colon wall and the labelling index of the colon mucosa were investigated in Wistar rats. Rats received sub‐cutaneous (s.c.) injections of AOM once a week for 10 weeks, and throughout 35 weeks were also given intraperitoneal (i.p.) injections of 6‐OHDA. Prolonged administration of 6‐OHDA was found to cause a significant reduction in the incidence and number of colon tumors. However, it had no influence on the histological features or depths of involvement of colon tumors and/or adenocarcinomas. Its administration also caused significant decreases in the NE concentration in the colon wall and in the labelling index of the colon mucosa. Our findings indicate that 6‐OHDA has a protective effect against colon carcinogenesis, and that the activity of the sympathetic nervous system may have an important influence on colon carcinogenesis.
Tumor‐cell motility and invasion within tumors determined by applying computer simulation to histologic patterns
Authors: Smolle Josef , Grimstad Ivar Amund
Published: February 2007

Proliferation and motility are crucial prerequisites for tumorcell invasion in vivo. While proliferation can be assessed in situ by a variety of methods, the measurement of motility is largely restricted to in vitro models. In previous studies, computer simulations of tumor growth strongly indicated that a close relationship exists between tumor‐cell motility on the one hand and the resulting morphological pattern on the other. Moreover, estimates of motility parameters can be based on image analysis of the particular pattern. The objective of the present study was to examine whether tumor‐cell populations differing in their in vitro motility produce particular patterns in vivo similar to those predicted by the computer simulations, and whether the motility estimates derived from these patterns are consistent with the in vitro motility results. This was done using murine fibrosarcomas grown in syngeneic animals from various cell lines which had been selected for and confirmed to show greatly increased speeds of motility in vitro relative to the unselected parent cell population. Computer simulations coupled with image analysis of the various variant tumors showed that the calculated motility of tumor cells within the different tumors agreed well with the relative levels of tumor‐cell motility observed in vitro. Our results thus show that the computer simulation method, along with histological analysis, produced reliable estimates of tumor‐cell motility within tumors.
Infrequent mutation of the ras genes in skin tumors of xeroderma pigmentosum patients in Japan
Authors: Ishizaki Kanji , Tsujimura Tohru , Nakai Masanao , Nishigori Chikako , Sato Kenji , Katayama Shoichi , Kurimura Osamu , Yoshikawa Kunihiko , Imamura Sadao , Ikenaga Mituo
Published: February 2007

By using PCR amplification and oligonucleotide mismatch hybridization, base‐substitution mutations of the ras genes in 26 skin tumors of Japanese xeroderma pigmentosum (XP) patients were studied. Thin sections of tumor tissues which were fixed and embedded in paraffin blocks were used in this study. After analyzing codons 12, 13 and 61 of the H‐, K‐ and N‐ras genes by using 66 oligomer probes, we detected only one mutation of the K‐ras gene at codon 61 in one tumor sample. All the other tumors were therefore considered not to have a mutation in the ras genes. These results suggest that mutations of the ras genes are not particularly associated with skin tumors of Japanese XP patients.
Identification and immunochemical characterization of IgA in sera of patients with mammary tumors
Authors: Chagnaud J. L. , Faiderbe S. , Geffard M.
Published: February 2007

It has been reported that several types of human cancer are associated with elevated levels of class‐A immunoglobulins (Ig) and IgA‐containing immune complexes. Moreover, most previous work has come up against the lack of IgA reactivity for chemically defined antigen (Ag). To overcome this, we first evaluated possible immunological binding in sera of patients with mammary tumors or malignant hematologic diseases and controls on a mouse monoclonal anti‐idiotypic antibody (Ab2), internal image of conjugated benzo(a)pyrene (BP) coated on well plates. Using this indirect ELISA, a statistically highly significant immunological binding was found in sera of patients with mammary tumors of every grade, type and size. This immunological binding was linked to the IgA isotype. Second, we performed competition experiments between a BP conjugate coated on well‐plates and anti‐anti‐“BP‐like” antibodies (Ab) previously incubated with rabbit idiotypic antibodies (Ab 1) directed against conjugated BP. A part of these anti‐anti‐BP‐ like Ab, raised in rabbits immunized with human IgA of patients with mammary tumors, recognized the Ag‐combining site of polyclonal Ab 1, previously developed in a rabbit immunized with BP conjugates. It appears that part of the human Ig from sera of patients with mammary tumors shares common id‐ iotopes with rabbit polyclonal Ab 1 raised against conjugated BP.
Fatty‐acid composition of breast and iliac adipose tissue in breast‐cancer patients
Authors: Chajes Véronique , Niyongabo Théodore , Lanson Monique , Fignon Alain , Couet Charles , Bougnoux Philippe
Published: February 2007

In order to determine to what extent the fatty‐acid composition of breast adipose tissue is representative of the body‐fat composition in breast carcinoma, we compared the fatty‐acid composition of breast adipose tissue to that of iliac fat in breast‐cancer patients. Triglycerides from the 2 sites were purified by thin‐layer chromatography and fatty‐acid composition was determined by capillary gas chromatography. Compared with iliac fat, mammary fat was higher in saturated (33.2 ± 3.9 vs. 24.4 ± 1.6%;p= 0.0001) and lower in mono‐ unsaturated (48.0 ± 2.2 vs. 54.8 ± 2.7%;p= 0.0001) and poly‐ unsaturated fatty acids (16.6 ± 3.7 vs. 18.0 ± 3.l%;p= 0.0001). A positive correlation was found between the 2 sites for linoleate (r= 0.95;p= 0.0003), alpha‐linolenate (r= 0.83;p= 0.01), palmitate (r= 0.78;p= 0.02) and palmitoleate (r= 0.76;p= 0.02). No relationship was observed for stearic and oleic acids. We conclude that breast and iliac fat differ with regard to fatty‐acid composition. The interpretation of fatty‐ acid composition of the body stores in breast‐cancer patients, as an indicator of long‐term intake of dietary fat, should take into account the sampling site of stored lipids.
Combination therapy with thymosin α1 potentiates the anti‐tumor activity of interleukin‐2 with cyclophosphamide in the treatment of the lewis lung carcinoma in mice
Authors: Mastino Antonio , Favalli Cartesio , Grelli Sandro , Rasi Guido , Pica Francesca , Goldstein Allan L. , Garaci Enrico
Published: February 2007

In this study we have investigated the effects of thymosin α1 (Tα1) and interleukin‐2 (IL‐2), singly or in combination with cyclophosphamide (CY), on tumor growth, survival and cytotoxicity in C57BI/6NCrlBR mice with Lewis lung carcinoma (3LL). Combined administration of Tα1 plus IL‐2, after CY treatment, was much more effective than use of each biological response modifier (BRM) alone, and induced complete tumor regression in all of the mice studied. Combination immunotherapy alone without CY only slightly reduced the rate of tumor growth, and these results are in accordance with previous studied which showed that the 3LL carcinoma is resistant to cytokines. Combined chemo‐immunotherapy also increased the cytotoxicity of spleen cells and markedly enhanced long‐term survival in all treated animals. Depletion of immune cells, using either total‐body sub‐lethal irradiation (400 rads) or antibodies directed against T‐cell (anti‐CD4 and CDS) or NK‐cell (anti‐asialo GMI) populations, abolished the positive response to combination therapy. Histological analysis of the tumors obtained from mice treated with combination chemo‐immunotherapy revealed a high number of infiltrating lymphoid cells surrounding a well‐circumscribed area of necrosis consisting solely of dead cells. Our studies show that Tα1 potentiates IL‐2‐induced cytotoxic activities in vitro as well in vivo, and that these compounds have a powerful anti‐tumor action when associated with chemotherapy.
Lifetime consumption of alcoholic beverages, tea and coffee and exocrine carcinoma of the pancreas: A population‐based case‐control study in The Netherlands
Authors: Bueno Mesquita H. B. De , Maisonneuve P. , Moerman C. J. , Runia S. , Boyle P.
Published: February 2007

From 1984 to 1988 a population‐based case‐control study was carried out in the Netherlands, in collaboration with the International Agency for Research on Cancer, to examine the possible relationship between the habitual lifetime consumption of alcohol, coffee and tea and exocrine pancreatic carcinoma in 176 cases and 487 controls. An interviewer‐administered questionnaire was used to ascertain major life events and obtain estimates of consumption (ever‐never) and frequency of consumption throughout life. Logistic regression analyses yielded odds ratios adjusted for age, sex, response status, smoking, dietary intake of energy and vegetables and of alcoholic or non‐alcoholic drinks. When compared with data from non‐drinkers, the cumulative lifetime consumption of all types of alcohol in grams of ethanol (ORs 1.00, 0.97, 0.93, 1.25, p trend 0.55), beer, spirits, red wine and fortified wine was not related to risk. The consumption of white wine was inversely associated with risk (OR 0.41, 95% Cl 0.24–0.70). The uniformly reduced risk estimates for the lifetime number of drinks of white wine were based on small numbers (ORs 1.00, 0.44, 0.25, 0.40, p trend 0.001). When compared with data from non‐drinkers, our findings suggest an inverse dose‐response relationship for the lifetime consumption of coffee (ORs 1.00, 0.72, 0.37, 0.58, p trend 0.06), whereas lifetime consumption of tea and of ground, instant and decaffeinated coffee was not associated with risk. The absence of an effect of lifetime consumption of decaffeinated coffee may be due to the small numbers of subjects. These results further strengthen existing evidence against a positive association between consumption as well as lifetime consumption of (sources of) alcohol, tea or coffee and the development of exocrine pancreatic cancer.
p53 allele losses, mutations and expression in breast cancer and their relationship to clinico‐pathological parameters
Authors: Thompson A. M. , Anderson T. J. , Condie A. , Prosser J. , Chetty U. , Carter D. C. , Evans H. J. , Steel C. M.
Published: February 2007

The p53 locus on the short arm of chromosome 17 at 17p 13.1 was examined for loss of heterozygosity, mutation, mRNA and protein expression in 60 primary breast cancers. Allele loss around the p53 locus was detected in 19/45 informative tumours (42%). p53 mutations in the evolutionarily conserved exons 5 to 9 were detected in 17/60 (28%) by amplification mismatch and confirmed by direct DNA sequencing. p53 mRNA expression was detected by Northern blot in 36/59 (61%) of tumours, and p53 protein expression using antibody 1801 on frozen‐tissue sections in 13/44 of the tumours examined. p53 mutation was significantly associated with oestrogen‐receptor‐poor tumours (p < 0.01) and hence with poor prognosis, but not with other clinical or pathological parameters. There was no statistical correlation between loss of heterozygosity around the p53 locus at 17p 13.1 and p53 mutation. Furthermore, p53 mutation was not associated with p53 expression detected by immunohistochemical staining with antibody 1801 or as p53 mRNA. In addition, events on 17p (allele losses, p53 mutation, p53 expression) were independent of c‐erb B‐2 expression. In breast cancer, by contrast with colorectal, lung and ovarian cancer, there appears‐to be no clear association between p53 DNA abnormalities and p53 expression.
Chromosomal damage in urothelial cells from egyptians with chronic Schistosoma haematobium infections
Authors: Rosin Miriam P. , Anwar Wagida
Published: February 2007

The most common cancer in Egypt is urinary‐bladder carcinoma, which is strongly associated with infection with Schistosomo haematobium. The object of this study was to determine whether infection with this parasite resulted in an increase in chromosomal breakage in the urothelium. Urine samples were collected from 37 Egyptian farmers with S. haematobium ova in their urine and from 32 non‐infected males attending the same village clinic. The urine was centrifuged and the urothelial cells present in the sediment were assayed for the presence of micronuclei, a quantitative indicator of chromosomal breakage. Micronucleus frequencies were significantly higher in the infected group (mean frequency, 0.97 ± 0.12%) than among controls (mean frequency, 0.12 ± 0.04%, p < 0.001). There was a trend towards an increase in micronucleus frequencies in infected individuals who smoked (10 of the 37 subjects) compared with those who were non‐smokers, although this effect was not significant (p = 0.12). Bladder infection was associated with a 6.8‐fold increase in micronucleus frequencies among non‐smokers. In a pilot study, 11 patients were treated with praziquantel, an anti‐schistosomal agent. Mean micronucleus frequencies were reduced significantly (before treatment, 1.27 ± 0.16%; after treatment, 0.30 ± 0.16%, p < 0.001), thus supporting a direct involvement of the infection in increased chromosomal breakage in the urothelium.
Human papillomavirus infection in esophageal squamous‐cell carcinoma in western countries
Authors: Benamouzig R. , Pigot F. , Quiroga G. , Validire P. , Chaussade S. , Catalan F. , Couturier D.
Published: February 2007

Recent studies have suggested that esophageal HPV infection could be a risk factor for esophageal squamous‐cell carcinoma. The aims of our study were to assess the presence of HPV esophageal infection among French patients with esophageal squamous‐cell carcinoma and to compare the prevalence of this infection among control patients exposed to similar known risk factors (alcohol and tobacco) and among non‐exposed control patients. All patients had the following investigations: serum immunoglobulin level, T‐lymphocyte sub‐sets, cutaneous anergy test and endoscopy with biopsies from tumoral and normal areas. Three different methods were used for HPV‐infection diagnosis: histological score, in situ hybridization intended for detection of HPV types 6, 11, 16, 18, 31 and 33, and dot blot intended for detection of HPV types 6/11 and 16/18. Five out of 12 patients with esophageal carcinoma had HPV esophageal infection. This infection did not result from impaired immune status. The most frequently observed types are HPV 16/18. None out of 17 exposed controls and only i out of 7 non‐exposed controls had HPV esophageal infection (p < 0.01). HPV infection may be implicated in the development of esophageal squamous‐cell carcinoma in association with known risk factors.
Effective combination chemo/hormonal therapy for malignant melanoma: Experience with three consecutive trials
Authors: McCiay Edward F. , Mastrangelo Michael J. , Berd David , Bellet Robert E.
Published: February 2007

Our experience with the combination of dacarbazine, carmustine, cisplatin with and without tamoxifen is reported. In our initial study, with all 4 drugs, we had an overall response rate of 50% with a complete response rate of 15%. Due to a high incidence of deep venous thrombosis and the lack of effectiveness of tamoxifen as a single agent, we deleted tamoxifen from the regimen and treated another 20 patients. Surprisingly, the response rate decreased to 10%. We then re‐incorporated tamoxifen into the regimen and treated 25 additional patients. In this third group of patients we experienced an objective response rate of 52% with a complete response rate of 8%. Overall, 65 patients have been treated: 45 with and 20 without tamoxifen. Twenty‐three (51%) patients treated with tamoxifen have responded, with 5 (11%) patients achieving a complete response. Only 2 (10%) patients treated without tamoxifen have responded. Despite the improvement in the response rate, a corresponding increase in survival has not been seen. Patients treated with tamoxifen had a mean survival of 10.8 (SD 13.6) months compared with a mean survival of 9.8 (SD 7.3) months for those treated without tamoxifen. The absence of survival advantage for the tamoxifen‐treated patients may be due to early failure in the central nervous system. In 48% of the responding tamoxifen‐treated patients, the first site of failure was the central nervous system, while systemic disease was still responding.
Correlation of L‐myc RFLP with metastasis, prognosis and multiple cancer in lung‐cancer patients
Authors: Kawashima Kazuko , Nomura Sachio , Hirai Hiroyuki , Fukushi Shuetsu , Karube Tsuyoshi , Takeuchi Kumiko , Naruke Tsuguo , Nishimura Susumu
Published: February 2007

For further study of the correlation of L‐myc restriction‐fragment‐length polymorphism (RFLP) and metastasis of lung cancer to lymph nodes or other organs at the time of surgery, L‐myc RFLP was analyzed in 252 Japanese lung‐cancer patients. A close correlation between L‐myc RFLP and metastasis was confirmed in this large number of patients (p = 0.01). The correlation was particularly pronounced in cases of adenocarcinoma and squamous‐cell carcinoma. Poor prognosis (additional metastases after surgery) was observed in lung‐cancer patients with L‐S (identified as long and short bands produced with EcoRI) and S‐S type L‐myc RFLP. In addition, the death rate of lung‐cancer patients with the L‐S and S‐S types was greater than that of those with the L‐L type. Lung‐cancer patients of the L‐S and S‐S types had almost 4 times higher incidence of multiple cancer in the lung, pharynx and other organs than those with the L‐L type. Our results indicate that, in patients with lung cancer, genetic disposition with respect to the L‐myc gene influences the extent of metastasis, the incidence of multiple cancers and prognosis.
Distribution of individual components of basement membrane in human colon polyps and adenocarcinomas as revealed by monoclonal antibodies
Authors: Ljubimov A. V. , Barter J. , Couchman J. R. , Kapuller L. L. , Veselov V. V. , Kovarik J. , Perevoshchikov A. G. , Krutovskikh V. A.
Published: February 2007

Double‐label immunofluorescence was used to monitor basement‐membrane composition and integrity in 22 human colon polyps, 36 adenocarcinomas and 2 metastases. Cryostat sections were stained with polyclonal anti‐laminin anti‐serum combined with monoclonal antibodies (MAbs) to all major basement‐membrane components (laminin, entactin/nidogen, collagen type IV and large heparan sulfate proteoglycan), as well as to keratin 8. In all adenocarcinomas, including mucinous, basement membranes were altered more at the invasive front than in the parenchyma. The degree of this alteration was inversely correlated with the level of tumor differentiation. An uncoordinated loss of basement membrane components (dissociation of markers), previously described by us in rat colon adenocarcinomas, was also found in human tumors. In the great majority of adenocarcinomas a pronounced stromal reaction was seen. It was manifested by the presence of fibrillar deposits of basement‐membrane components, mainly of collagen type IV and/or heparan sulfate proteoglycan. This reaction was never observed in polyps and may be derived from myofibroblasts reported to accumulate in colon cancer stroma. The combined use of antibodies to basement‐membrane components and to a specific keratin may constitute an adequate immunohistochemical test for the presence of invasion, and may be useful in the histologic analysis of polyps, especially in dubious cases.
Body mass at different ages and subsequent endometrial cancer risk
Authors: Levi Fabio , La Vecchia Carlo , Neori Eva , Parazzini Fabio , Franceschi Silvia
Published: February 2007

The relationship between body mass index (BMI) at different ages and subsequent endometrial‐cancer risk was investigated in a multicentre case‐control study conducted between 1988 and 1991 in Vaud, Switzerland, and Northern Italy on 272 histologically confirmed incident cases of endometrial cancer and 571 controls admitted to hospital for acute, non‐neoplastic conditions, unrelated to known or potential risk factors for endometrial cancer. The risk of endometrial cancer increased with increasing BMI in the 3rd decade of age (20 to 29 years), in the 5th decade (40 to 49 years) and in the 7th decade (60 to 69 years), although the risk estimates tended to be substantially higher at older ages: compared with women whose BMI (kg m−2) was < 20, the relative risks (RR) were 1.8 for BMI ± 25 at age 20 to 29, 2.7 for BMI ± 30 at age 40 to 49 and 3.8 at age 60 to 69. All the trends in risk were significant, except that for BMI at age 25 after allowance for current BMI. When data were examined in separate strata of current BMI, among women of normal body mass at diagnosis no significant effect of past overweight was observed. In contrast, among subjects overweight at diagnosis, there were significant direct relationships with BMI at ages 20 to 29 and 40 to 49. To reduce endometrial cancer risk, it is therefore important to avoid obesity in later middle and older age, and the benefit can be even greater for women who were overweight at younger age.
Regulation of leukocyte binding to endothelial tissues by tumor‐derived GM‐CSF
Authors: Fu Yang‐Xin , Cai Jian‐Ping , Chin Yee‐Hon , Watson Gordon A. , Lopez Diana M.
Published: February 2007

The adherence of leukocytes to endothelial cells is the first step in the migration of these cells into tumor tissues. Specific binding to the endothelial cells by leukocytes is mediated by the development and maintenance of adhesion molecules on the endothelium; however, the mechanisms of leukocyte traffic into tumors and of their interactions with neoplastic tissue are not clearly understood. The infiltration of leukocytes occurs in most spontaneous and transplanted solid tumors and we have previously reported that not only are murine mammary tumors heavily infiltrated by leukocytes but tumor‐derived factors alter the development and function of leukocytes in tumor‐bearing mice. We now present evidence that a tumor‐derived cytokine, namely granulocyte‐macrophage‐colony‐stimulating factor, appears to be of importance in the regulation of leukocyte binding to endothelial cells. The data suggest that tumor‐derived factors may influence leukocyte trafficking within tumor tissue.
Cell phenotype (CD23)‐dependent variation in EBV genome copy numbers within lymphoblastoid cell lines (LCL)
Authors: Wendel‐Hansen Vidar , Tao Wen , Ericson Mats , Klein George , Rosen Anders
Published: February 2007

Three Epstein‐Barr‐virus‐transformed lymphoblastoid cell lines (LCL) were analysed on the basis of their CD23 expression. Levels of EBV‐DNA were compared in the positive and negative subpopulations. Two lines were further analysed with regard to EBNA, cytoplasmic immunoglobulin (clg) and lytic (EA/VCA) protein expression. Both subpopulations had a similar MHC class‐11 transcription, but the CD23− subpopulation had a lower plating efficiency and a lower rate of DNA synthesis. In the B6, NAD50 and 0467.3 cell lines, CD23− cells contained 2 ± 0.2–6.4 ± 3.0 times less EBV DNA than the corresponding CD23+ population. EBNA was expressed in 81 ± 4.2%‐93 ± 3.8% of the CD23+ cells and in 0–46 ± 8.0% of the CD23− cells. No CD23+ cells in B6 or NAD50 contained any EA/VCA, while 19 ± 2.8%‐24 ± 4.2% of the CD23− cells were positive for the lytic‐cycle‐associated antigens. Of the CD23− cells, 70 ± 8.6%‐86 ± 6.0% were positive for cytoplasmic immunoglobulin compared to 14.7 ± 2.7%‐14.9 ± 1.8% in the corresponding CD23+ population. We have previously shown that only 18% of the clg‐positive cells were EBNA‐positive in the B6 line compared to 94% in the clg population. This was open to 2 alternative interpretations: loss of EBV genomes from a fraction of the cells with subsequent differentiation to secretory immunoglobulin production, or down‐regulation of EBNA expression in differentiating, EBV‐genome‐positive cells. Our present findings speak for the first alternative, indicating that a certain proportion of the cells may lose their EBV genomes in both long‐established and freshly transformed LCLs. This is accompanied by a reduced percentage of EBNA‐positive cells, the disappearance of at least one activation marker (CD23) associated with the virally induced blast transformation, and an increased synthesis of clg.
Effects of CPT‐11 in combination with other anti‐cancer agents in culture
Authors: Kano Yasuhiko , Suzuki Kenichi , Akutsu Miyuki , Suda Keiichi , Indue Yoshiharu , Yosnida Minoru , Sakamoto Shinobu , Miura Yasusada
Published: February 2007

CPT‐11, 7‐ethyl‐10‐[4‐( 1 ‐piperidino)‐1 ‐piperidino]carbonyloxy camptothecin, is a newly developed water‐soluble camptothecin derivative now undergoing phase‐II evaluation. In an attempt to establish whether the combination of CPT‐11 with other standard anti‐cancer agents would be of any benefit, we studied the effects of CPT‐11 in combination with 11 other anti‐cancer agents on a human T‐cell leukemia cell line, MOLT‐3, in culture. We used both CPT‐11 and SN‐38 (active substance of CPT‐11 in vivo), for our study. Cells were incubated for 3 days in the presence of 2 drugs (CPT‐11 or SN‐38 and another drug) and cytotoxic effects were determined by MTT assay. The effects of drug combinations on ID50 were analyzed, by an improved isobologram method. Supra‐additive and marginal supra‐additive effects (synergism) were observed for CPT‐11 in combination with cisplatin, cytosine arabinoside and mitomycin C. Additive effects were observed for its combination with amsacrine, bleomycin, doxorubicin, etoposide, 5‐fluorouracil, mitoxantrone and vincristine. Alternate sub‐additive and protective effects (antagonism) were observed for CPT‐11 in combination with methotrexate. Similar tendencies were observed for SN‐38 in combination with other agents. These results suggest that CPT‐11 in simultaneous administration with a majority of anti‐cancer agents has an advantage for cytokilling. Of these agents, cisplatin, cytosine arabinoside and mitomycin C are most suitable for simultaneous administration with CPT‐11.
An anti‐doxorubicin monoclonal antibody modulates kinetic and dynamic characteristics of the drug
Authors: Sardini Alessandro , Villa Elena , Morelli Daniele , Ghione Mario , Ménard Sylvie , Colnaghi Maria Ines , Balsari Andrea
Published: February 2007

A monoclonal antibody (MAb) directed against doxorubicin (DXR), denominated MAD11, was found to exert an antidotal action by modulating the kinetic and dynamic characteristics of the drug. In vitro, MAD11 has been found to reduce the cytotoxicity of DXR and the drug uptake on spleen lymphocytes more efficiently than on tumor cells (P388 leukemia cells). In vivo, the anti‐DXR MAb modified the drug distribution; the drug uptake was found to be reduced in the intestine and myocardial tissues and increased in the tumor, liver and spleen. In mice treated with DXR, the administration of anti‐DXR MAb exerted an antidotal activity which was proved by the reduction in body‐weight loss and mortality. In contrast, the therapeutic efficacy of the drug in P388‐tumor‐bearing mice was not influenced by the anti‐DXR MAb.
Pre‐treatment of a human T‐lymphoblastoid cell line with L‐asparaginase reduces etoposide‐induced DNA strand breakage and cytotoxicity
Authors: Shimizu Tsunehiro , Kubota Masaru , Adachi Souichi , Sano Hirohiko , Kasai Yasufumi , Hashimoto Hisako , Akiyama Yuichi , Mikawa Haruki
Published: February 2007

The effect of L‐asparaginase (L‐asp) pre‐treatment on etoposide‐induced DNA strand breakage and cytotoxicity was investigated. In a T‐lymphoblastoid cell line, Molt 4, etoposide‐induced DNA strand breaks, DNA‐protein cross‐links and cytotoxicity were reduced by pre‐treatment with L‐asp for 15 hr, but it did not cause these changes in a promyelocytic‐leukemia cell line, HL‐60, which is less sensitive than Molt 4 to L‐asp. However, pre‐treatment of Molt 4 cells with L‐asp did not significantly alter the accumulation of [3H]‐etoposide. Cell‐cycle analyses snowed an increase in G1‐phase cells, a significant decrease in both S‐phase cells and G2/M‐phase cells pre‐treated with L‐asp in Molt 4 cells, but L‐asp exposure did not result in any significant changes in HL‐60 cells. On the other hand, L‐asp pre‐treatment did not affect topoisomerase‐I (Topo‐I) inhibitor, camptothecin (CPT)‐induced DNA strand breaks or toxicity in Molt 4 cells. Our data imply that a decrease in S‐ and G2/M‐ phase cells following L‐asp treatment may explain the reduction of etoposide‐induced DNA lesions and cytotoxicity in Molt 4 cells, since topoisomerase‐II (Topo‐II) content or activity is a function of cellular proliferation status.
in situ expression of the IL‐I‐α and tnf‐α genes by reed‐sternberg cells in Hodgkin's disease
Authors: Xerri L. , Birg F. , Guigou V. , Bouabdallah R. , Poizox‐Martin I. , Hassoun J.
Published: February 2007

The histopathologic pattern of tissues involved by Hodgkin's disease (HD) suggests excessive activation of environmental cells by cytokines released by Hodgkin‐Reed‐Sternberg (HRS) cells, which are considered as the neoplastic component of HD lesions. This hypothesis has been supported by many studies performed in vitro using HD cell lines. In this study, we have tried to demonstrate the cytokine‐producing cells in an environment as close as possible to the in vivo conditions, using in situ hybridization onto frozen sections of HD samples. [35S]‐labelled single‐stranded RNA probes were prepared by transcribing human cDNA fragments of the TNF‐α and IL‐1 α genes sub‐cloned into appropriate vectors. A total of 19 specimens of HD lesions, including 7 cases of nodular sclerosing (NS) type and 12 cases of mixed cellularity (MC), were tested with both types of probes. Clinical stages included stage I (6 cases), stage II (4 cases), stage III (6 cases) and stage IV (3 cases). TNF‐α and/or IL‐I α expression was observed in 12 among 19 HD cases. However, neither the histological type nor the clinical status of the patients was correlated with the profile of cytokine secretion. Most of the cytokine‐producing cells could be identified as HRS cells due to their morphological appearance. In 3 cases, simultaneous analysis by immunohistochemistry and in situ hybridization showed that IL‐1 α/TNF‐α mRNA‐producing cells simultaneously expressed the CD30 antigen, thereby confirming the HRS nature of these cells.