bluuebunny/crossref_metadata_2025 huggingface dataset:
Familial aggregation of tumors and detection of hereditary non‐polyposis colorectal cancer in 3‐year experience of 2 population‐based colorectal‐cancer registries
Authors: Modica Salvatore , Roncucci Luca , Benatti Piero , Gafà Lorenzo , Tamassia M. Grazia , Dardanoni Luigi , de Leon Maurizio Ponz
Published: February 2007

The clinical data of 2 population‐based registries, located in areas with different incidence rates of colorectal cancer, were used in order to assess the role of familial factors in the pathogenesis of these tumors. The occurrence of tumors in family members was investigated in 389 subjects with colorectal cancer registered in Modena (Northern Italy, an area characterized by a high incidence of colorectal malignancies) between 1984 and 1986; similar information was obtained in 213 patients with tumors of the large bowel registered in Ragusa (Sicily, Southern Italy, an area of similar magnitude and with low incidence rates for these tumors) in the 3‐year period 1988 to 1990. In both series, colorectal cancer occurred significantly more often among relatives of patients. Controls were patients of the same sex and age (±5 years) hospitalized during the study periods, but not for gastrointestinal or neoplastic diseases. There were 89 cancer cases (3.1%) among 2,851 relatives of patients in Modena, vs. 17 cases among 1,744 relatives (1.0%) in Ragusa (p < 0.01). Apart from colorectal cancer, there was no excess of other types of tumors in patients' families (in both series). During the 3 years of registration, 17 cases of hereditary non‐polyposis colorectal cancer (HNPCC, or Lynch syndrome) were diagnosed in Modena; in contrast, this syndrome was more rare in Ragusa (one case only during 3 years of observation). Similarly, many more families with clinical suspicion of HNPCC were recorded in Northern regions (44 vs. 10). Although incidence rates of colorectal cancer are appreciably higher in Northern than in Southern Italian regions, the excess of this cancer type among close relatives is similar. However, fullblown HNPCC or suspected Lynch syndrome were significantly more frequent in Northern Italy. © 1995 Wiley‐Liss, Inc.
Among 17 inducers of differentiation only sodium butyrate causes a permanent down‐regulation of c‐myc in Burkitt's lymphoma
Authors: Rottleb Christoph , Bornkamm Georg W. , Polack Axel
Published: February 2007

De‐regulation of c‐myc by chromosomal translocation is one crucial step for the development of Burkitt's lymphoma. The de‐regulation is caused through juxtaposition of c‐myc with one of the 3 immunoglobulin loci. We have reported earlier that treatment of Burkitt's lymphoma cells with n‐butyrate causes transcriptional down‐regulation of c‐myc expression. Because of the possible therapeutic implication of this result, we looked for other compounds which, on the one hand, might be applicable in vivo and, on the other hand, might cause down‐regulation of c‐myc expression in Burkitt's lymphoma cells. Since n‐butyrate is known to induce differentiation, we have examined other differentiation inducers of different chemical nature for their ability to reduce c‐myc expression in Burkitt's lymphoma cells. Many of the substances tested caused down‐regulation of c‐myc expression, which, however, was transient except for n‐butyrate. Three types of compounds proved to be particularly active: polar planar compounds (e.g., dimethylsulfoxide), heterocyclic compounds (e.g., hypoxanthine), and short‐chain fatty acids (e.g., n‐butyric acid). The action of n‐butyrate on c‐myc supression was exceptional not only in not being transient, but also in being allele‐specific: it down‐regulated the translocated allele without affecting the normal one. Medium transfer experiments revealed that neither degradation of the active compound nor an intracellular resistance mechanism can fully account for the reversibility of c‐myc down‐regulation after treatment with the transiently acting polar planar compounds. © 1995 Wiley‐Liss, Inc.
Involvement of a transforming‐growth‐factor‐β‐like molecule in tumor‐cell‐derived inhibition of nitric‐oxide synthesis in cerebral endothelial cells
Authors: Murata Jun‐Ichi , Corradin Sally Betz , Felley‐bosco Emanuela , Juillerat‐Jeanneret Lucienne
Published: February 2007

Nitric oxide (NO) has been shown to exert cytotoxic effects on tumor cells. We have reported that EC219 cells, a rat‐brain‐microvessel‐derived endothelial cell line, produced NO through cytokine‐inducible NO synthase (iNOS), the induction of which was significantly decreased by (a) soluble factor(s) secreted by DHD/PROb, an invasive sub‐clone of a rat colon‐carcinoma cell line. In this study, the DHD/PROb cell‐derived NO‐inhibitory factor was characterized. Northern‐blot analysis demonstrated that the induction of iNOS mRNA in cytokine‐activated EC219 cells was decreased by PROb‐cell‐conditioned medium. When DHD/PROb cell supernatant was fractionated by affinity chromatography using Con A‐Sepharose or heparin‐Sepharose, the NO‐inhibitory activity was found only in Con A‐unbound or heparin‐unbound fractions, respectively, indicating that the PROb‐derived inhibitory factor was likely to be a non‐glycosylated and non‐heparin‐binding molecule. Pre‐incubation of DHD/PROb‐cell supernatant with anti‐TGF‐β neutralizing antibody completely blocked the DHD/PROb‐derived inhibition of NO production by EC219 cells. Addition of exogenous TGF‐β, dose‐dependently inhibited NO release by EC219 cells. The presence of active TGF‐β in the DHD/PROb cell supernatant was demonstrated using a growth‐inhibition assay. Moreover, heat treatment of medium conditioned by the less invasive DHD/REGb cells, which constitutively secreted very low levels of active TGF‐β, increased both TGF‐β activity and the ability to inhibit NO production in EC219 cells. Thus, DHD/PROb colon‐carcinoma cells inhibited NO production in EC219 cells by secreting a factor identical or very similar to TGF‐β. © 1995 Wiley‐Liss, Inc.
Estrogen‐induced anchorage‐independence in human endometrial stromal cells
Authors: Xu Li‐Hui , Rinehart Clifford A. , Kaufman David G.
Published: February 2007

Estrogens are important etiologic agents for most gynecologic malignancies, and chronic exposure to estrogen that is unopposed by progestins conveys the greatest risk. Treatments with estrogen facilitate the process of malignant transformation in rodents, but relatively few studies of estrogen‐induced carcinogenesis have been performed using human cells. Most malignancies in estrogen‐responsive tissues arise from epithelial cells, but an increasing body of evidence emphasizes the role of stromal cells as mediators of the effects of estrogens on epithelial cells. Our studies were designed to assess estrogens as carcinogens for human endometrial stromal cells and to provide a basis for studies of the role of stroma in estrogen‐induced carcinogenesis in humans. Acute treatments with the estrogens diethylstilbestrol (DES), 17β‐estradiol E2 and β‐dienestrol enhance anchorage‐independent proliferation (AIP) of SV40‐immortalized human endometrial stromal cells in the rank order of DES > E2 > β‐dienestrol. The anti‐estrogenic compound tamoxifen inhibits DES‐induced AIP. The magnitude of DES‐induced AIP increases with prolonged duration of treatment. After 11 months of chronic treatment with 0.1 nM DES, AIP was 20‐fold higher than in vehicle‐treated control cultures. Expression of the estrogen receptor was altered by treatments with DES in parallel with increased capacity for AIP. These conditionally immortal human endometrial stromal cells appear to be a good model for estrogen‐induced transformation of human cells. © 1995 Wiley‐Liss, Inc.
Cell‐cell and cell‐collagen interactions influence gelatinase production by human breast‐carcinoma cell line 8701‐BC
Authors: Minafra Salvatore , Giambelluca Carola , Andriolo Maria , Pucci‐Minafra Ida
Published: February 2007

We previously produced evidence that the human mammary‐carcinoma cell line 8701‐BC expresses several metalloproteinases (MMP‐1, ‐2, ‐9, and ‐10) and their tissue inhibitors. In order to obtain a better understanding of the environmental control over gelatinolytic activities, we have tested the enzyme production of 8701‐BC cells, at time intervals after plating on different collagen substrates, i.e., types I, III, IV, V and OF/LB, used as films in culture dishes. Proteinase activities, released in the conditioned culture media, were tested by zymography on SDS‐PAGE, and by quantificative analyses, using 14C carboxy‐methylated transferrin as substrate in a liquid incubation medium. Enzymatic activities varied with time and were inversely related to cell densities, with minimum values at cell confluence. The enzymatic activity was positively supported by collagen substrates, with a maximal increase in activity when OF/LB collagen was used. In addition to the known MMPs, we found a proteinase with an Mr of about 20 kDa, which displayed higher activity at 48 hr after cell plating and gradually decreased with cell increment. In contrast to the other MMPs, this proteinase is inhibited by soybean trypsin inhibitor, but it does not display a complete identity with trypsin, since it does not digest casein and is not inhibited by other serine proteinase inhibitors. © 1995 Wiley‐Liss, Inc.
Different risk groups in node—negative breast cancer: Prognostic value of cytophotometrically assessed DNA, morphometry and texture
Authors: Aubele Michaela , Auer Gert , Voss Andreas , Falkmer Ursula , Rutquist Lars‐Erik , Höfler Heinz
Published: February 2007

Feulgen—stained imprints and fine‐needle aspirates from 528 lymph‐node‐negative breast cancers were investigated by means of an image analysis system. Several DNA, morphometric and textural parameters were evaluated for each patient. The prognostic value of the parameters was investigated by multivar‐iate Cox regression analysis. As prognostic criteria, a distant recurrence‐free survival of 5 years and an overall survival of 8 years were considered. In multivariate analyses the anisokaryo‐sis (standard deviation of nuclear radius, Rad_SD) was the strongest parameter in predicting the clinical course of node‐negative patients. This was followed by a textural parameter (run‐length, NR2_M) and the tumor size (pT). The DNA histogram type could also add prognostic information concerning distant recurrence‐free survival, but not overall survival. In both approaches a multivariate prognostic factor was calculated for each of the node‐negative patients by a linear combination of the selected variables. Using this factor, patients could be split into 5 subgroups with significantly different risks of distant metastases. Thus, a low‐risk subgroup, with a 5‐year distant recurrence rate of only 3%, and a subgroup with a considerably higher risk and a distant recurrence rate of 35%, could be distinguished. In survival analysis the low‐risk group of node‐negative patients showed an 8‐year death rate of only 3%, whereas in the high‐risk group 30% of the patients had died at 8 years. Thus DNA, morphometric and textural parameters can provide powerful prognostic information in node‐negative breast carcinomas. The multivariate combination of the relevant variables may allow a better selection of those node‐negative patients with a proven good prognosis, and of those who are at risk of distant recurrence and therefore may benefit from adjuvant treatment.
Dietary fat and the risk of breast cancer: A prospective study of 25,892 Norwegian women
Authors: Gaard Maria , Tretli Steinar , Løken Elin B.
Published: February 2007

In this prospective study, the relationship between energy and fat consumption and the risk of breast cancer was examined. Between 1977 and 1983, 31, 209 Norwegian women, 20 to 54 years of age attended a health screening. The attendees were given a food‐frequency questionnaire to be completed at home, and this was returned by 25,892 (83%). During the 7 to 13 years of follow‐up, 248 cases of breast cancer were identified for analysis by linkage to the Norwegian Cancer Registry. The relative risk of women who ate meat more than 5 times a week, as compared with those who consumed meat twice or less than twice a week, was 2.44. Consumers of 0.75 litres or more of full‐fat milk daily had a relative risk of 2.91 compared with those who consumed 0.15 litres or less. A positive relationship was found between those reporting the highest quartile of mono‐unsaturated fat consumption and the risk of breast cancer. The main foods contributing to the mono‐unsaturated fat index were edible fats, meat and milk.
Descriptive epidemiology of lymphoid and haemopoietic malignancies in Bangalore, India
Authors: Nandakumar Ambakumar , Anantha Narayanappa , Venugopal Thalagavadi , Reddy Sreerama , Padmanabhan Bapsy , Swamy Kumara , Doval Dinesh , Ramarao Clementina
Published: February 2007

Lymphoid and haemopoietic malignancies as a group constitute one of the important cancers in India, as elsewhere in the world. While information on incidence and mortality of these cancers, and that on survival, are available from most developed countries, there areveryfew reports describing this experience in developing ones. Population‐based cancer registration commenced in Bangalore, India, in January 1982, under the auspices of the Indian Council of Medical Research. This source provides fairly complete and reliable incidence data, but, in order to obtain mortality and survival information, active follow‐up involving visits of homes of patients was undertaken. Between 1982 and 1989, 1397 cases of lymphoid and haemopoietic malignancies were registered in the Bangalore cancer registry, giving an age‐adjusted incidence rate of 7.7 and 4.8 per 100,000 in males and females respectively. Active follow‐up provided mortality/survival information in 1267or90.7% of these cases. The overall observed 5‐year survival for these cancers combined (both sexes) was 26%, and relative survival 28.4%. The 5‐year survival rate was lower in all the individual lymphomas and leukaemias as compared with similar reports from the developed countries. Survival in Hodgkin's disease was influenced by clinical stage and age at presentation.
Differences in expression of metalloproteinases and plasminogen activators in murine melanocytes and B16 melanoma variants: Lack of association with In vitro invasion
Authors: Huuzer Jeannette C. , Uhlenkott Carey E. , Meadows Gary G.
Published: February 2007

We investigated in vitro chemotactic responses to fibronectin and laminin, invasion through reconstituted basement membrane (Matrigel) and secretion of matrix metalloproteinases and plasminogen activators by non‐tumorigenic Mel‐ab melano‐cytes; B16 melanoma; and the metastatic sublines, B16F1, B16F10 and B16BL6. In vitro chemotactic and invasive ability were not associated with in vivo metastatic potential. Secretion of various matrix‐degrading enzymes was not related to in vitro invasion. Conditioned media from all B16 melanoma sublines, but not from Mel‐ab cells, contained the Mr 92,000 pro‐gelatinase. The activated Mr 85,000 species was present only in conditioned media from Mel‐ab, B16 and B16F1 cells. Mel‐ab cells secreted copious amounts of the Mr 72,000 pro‐gelatinase, and the Mr 66,000 active form was also present in conditioned media. Secretion of the Mr 72,000 pro‐gelatinase by B16 melanoma sublines was markedly lower, and only conditioned media from B16 cells contained the activated Mr 66,000 form. Furthermore, cell lysates of Mel‐ab cells contained a Mr 67,000 metalloproteinase which was absent in the tumor cells. All cells secreted tissue plasminogen activator; however, the metastatic B16F1, B16F10 and B16‐BL6 cells also secreted urokinase plasminogen activator. Our results indicate that matrix metalloproteinase secretion by itself is not associated with tumorigenicity or metastatic potential. Secretion of urokinase plasminogen activator, and not tissue plasminogen activator, reflected the metastatic characteristics of the B16 melanoma tumor sublines.
In vivo inhibition of oestrone sulphatase and dehydroepiandrosterone sulphatase by oestrone‐3‐O‐sulphamate
Authors: Purohit A. , Williams G. J. , Roberts C. J. , Potter B. V. L. , Reed M. J.
Published: February 2007

Many tumours in endocrine‐sensitive tissues, such as the breast and endometrium, are hormone‐dependent and the hydrolysis of oestrone sulphate (EIS) to oestrone by oestrone sulphatase (EI‐STS) is a major source of oestrogen in such tumours. Oestrone‐3‐O‐sulphamate (EMATE) has been shown to be a potent EI‐STS inhibitor in vitro, and in this study its ability to inhibit enzyme activity in vivo was examined. EMATE was initially administered to female rats for 7 days, after which liver EI‐STS activity was measured. As EMATE also inhibits a related sulphatase in vitro, dehydroepiandrosterone sulphatase (DHA‐STS), its effect on the activity of this enzyme in vivo was also investigated. DHA‐STS has a pivotal role in regulating the synthesis of another steroid with potent oestrogenic properties, androstenediol. Administration of EMATE almost completely inhibited liver EI ‐STS (99%) and DHA‐STS (99%) activities and was active when given by the oral or subcutaneous routes. After a single dose of EMATE or following the cessation of multiple doses for 10 days, liver EI‐STS activity remained inhibited (>95%) for up to 7 and 10 days, respectively. Other compounds, such as 4‐hydroxytamoxifen and the “pure” anti‐oestrogen ICI 182,780, which are reported to inhibit EI‐STS activity in vitro, did not inhibit activity in vivo. In a preliminary study, EMATE, when injected over a 12‐day period, effectively reduced the growth of EI S‐stimulated nitrosomethyl‐urea‐induced mammary tumours in ovariectomised rats and inhibited tumour sulphatase activity in treated animals.
Is the apparent rise in cancer mortality in the elderly real? analysis of changes in certification and coding of cause of death in England and Wales, 1970–1990
Authors: Grulich Andrew E. , Swerdlow Anthony J. , Silva Isabel Dos Santos , Beral Valerie
Published: February 2007

The effect of changes in recording and coding of cause of death on trends in cancer mortality in England and Wales in persons aged 45 and over during 1970–1990 is reviewed. During this period, all‐cancer mortality rates increased only at ages over 75 in males and over 55 in females. Rises in cancer mortality were largely due to increases in cancer of lung, prostate and unspecified site in men, and of lung, breast and unspecified site in women. Death coding and certification artefacts were much larger in older persons. In those aged 75–84, a change in the position of recording cancer on the death certificate could potentially account for 46% of the recorded increase in prostate‐cancer mortality and 28% of the increase in breast‐cancer mortality. The decrease in recorded mortality from ill‐defined terminal events was far greater than the increase in cancer mortality in this age group. The rise in all‐cancer mortality in the elderly was partly due to an increase in lung‐cancer mortality, and data artefacts explained a large proportion of the increase in the other common specified cancers in those aged 75–84. The use of routine mortality statistics to chart progress against cancer lacks validity at older ages because of imprecision in certification of cause of death.
Distribution of extracellular and cytoplasmic domains of the α3 and α6 integrin subunits in solid tumors
Authors: Patriarca Carlo , Ivanyi Dagmar , Fles Daniëlle , De Melker Annemieke , Van Doornewaard Greet , Oomen Lauran , Alfano Rosa Maria , Coggi Guido , Sonnenberg Arnoud
Published: February 2007

Integrins play an important role in malignant transformation and the invasion of tumors. They mediate cell‐cell and cell‐matrix interactions and participate in transduction of signals across the plasma membrane, processes dependent on the extracellular and cytoplasmic domains of integrins. We studied a selection of solid tumors by immunohistochemistry using monoclonal antibodies (MAbs) against the extracellular domain and the cytoplasmic variants (A and B) of the α3 and α6 integrin subunits. The tissue‐specific expression of ecto‐ and cyto‐domains of α3 and α6 is maintained in a subset of breast, colon, kidney and parotid tumors. In a few breast tumors, there was a switch in variant expression in that α6B was detected instead of α6A in normal breast tissue. In many colon and parotid tumors, one of the variants of α6 was missing, while both were detectable in the corresponding normal tissues. In contrast, co‐expression of the α6 variants was found in some kidney tumors, whereas only one of the variants was detected in the normal tissue. In a minority of colon and kidney tumors, the cytodomains of α3 and α6 were undetectable and total absence of α3 and α6 was noted in a subset of breast, colon, kidney and parotid tumors. These observations show that expression of the integrin variants in tumors varies considerably and support the concept that changes in expression may contribute to malignant behavior.
Response to interferon therapy in patients with multiple myeloma correlates with expression of the Bcl‐2 oncoprotein
Authors: Sangfelt Olle , Österborg Anders , Grandér Dan , Anderbring Elisabet , Öst Åke , Mellstedt Håkan , Einhorn Stefan
Published: February 2007

The expression of the Bcl‐2 oncoprotein was studied in pre‐treatment bone‐marrow samples from 63 patients with multiple myeloma, using an immunohistochemistry technique. A variable expression of the Bcl‐2 protein was found in myeloma cells. 43% of the patients had strong expression of the Bcl‐2 protein in the malignant cells. Forty patients received α‐interferon, whereas 23 patients received melphalan/prednisone therapy. A significant association (p = 0.012) was found between high levels of Bcl‐2 expression in myeloma cells and resistance to interferon therapy. No such correlation was found in the melphalan/prednisone treated patients. The data indicate that over‐expression of Bcl‐2 may be a cause for resistance to interferon therapy in myeloma and that staining for Bcl‐2 expression in myeloma cells may have a predictive value for this treatment.
Variable expression of CD3‐ζ chain in tumor‐infiltrating lymphocytes (TIL) derived from renal‐cell carcinoma: Relationship with til phenotype and function
Authors: Tartour Eric , Latour Sylvain , Mathiot Claire , Thiounn Nicolas , Mosseri Véronique , Joyeux Isabelle , D'Enghien Catherine Dubois , Lee Renshiang , Debre Bernard , Fridman Wolf Herman
Published: February 2007

It has been reported that in mice and in humans, tumor‐infiltrating lymphocytes (TIL) may exhibit a defect in CD3‐ζ‐chain expression. Therefore, the level of CD3‐ζ was analyzed in TIL derived from patients with renal‐cell carcinoma, and its correlation with TIL phenotype and function was assessed. We identified 4 out of 13 tumor‐infiltrating lymphocytes derived from renal‐cell carcinoma, with a significant decrease in CD3‐ζ‐chain expression as compared with control peripheral‐blood lymphocytes. This defect was never found after culturing TIL with IL2. In one case, the low expression of ζ chain observed in TIL on day 0 was reversed when TIL were cultured with IL2. The ζ‐chain level did not seem to predict the growth of TIL in response to IL2. All the TIL, irrespective of the level of ζ‐chain expression, exhibited lower proliferative response when stimulated with PHA or anti‐CD3 MAb in comparison with normal peripheral‐blood mononuclear cells. Nevertheless, in this limited series of patients, a correlation was observed between the level of ζ‐chain expression and T‐cell infiltration (p = 0.02). After TIL stimulation with PHA or anti‐CD3, in contrast to IL2 or IFNγ production, a trend towards a relationship between TNF α induction and the level of ζ‐chain expression was observed.
Inhibition of processing of parathyroid hormone‐related peptide by anti‐sense furin: Effect in vitro and in vivo on rat leydig (H‐500) tumor cells
Authors: Liu Bin , Amizuka Norio , Goltzman David , Rabbani Shafaat A.
Published: February 2007

To attain full biological activity, the precursor pro‐parathyroid hormone‐related peptide (ProPTHRP) must be converted to the mature peptide PTHRP. We have examined the effect of inhibiting expression of the pro‐hormone convertase furin in H‐500 rat Leydig tumor cells on PTHRP production and action in vitro and in vivo. H‐500 Leydig tumor cells were stably transfected with a mammalian expression plasmid containing furin cDNA in an anti‐sense orientation. This resulted in inhibition of endogenous furin mRNA expression and of protein production as assessed by immunocytochemistry. These experimental cells secreted extended NH2‐terminal PTHRP forms with reduced adenylate cyclase‐stimulating activity. This was associated with a marked decrease in the proliferation of these tumor cells in vitro. Transfected and control cells were then implanted into male Fischer rats. Animals implanted with control cells became hypercalcemic. In contrast, animals implanted with experimental cells maintained near normal levels of plasma calcium. Experimental cells inoculated in vivo developed into tumors of significantly decreased volume compared to control cells and animal survival time was prolonged. Our results indicate that alteration of the processing of PTHRP can diminish the hypercalcemic endocrine actions of PTHRP and can reduce autocrine/paracrine effects of PTHRP on tumor cell growth both in vitro and in vivo. Furin may also exert a broader role in processing other factors required for tumor proliferation. Consequently, anti‐sense modulation of furin activity may be a potential modality for understanding the mechanism of neoplastic growth and progression.
Comparative expression of the psoriasin (S100A7) and S100C genes in breast carcinoma and co‐localization to human chromosome 1q21‐q22
Authors: Moog‐Lutz Christel , Bouillet Philippe , Régnier Catherine H. , Tomasetto Catherine , Mattei Marie‐Geneviève , Chenard Marie‐Pierre , Anglard Patrick , Rio Marie‐Christine , Basset Paul
Published: February 2007

Using differential screening of a breast cancer cDNA library, we isolated a cDNA encoding the psoriasin (S100A7) protein, previously identified in psoriatic epidermis. In the present study, we demonstrate that the psoriasin gene is expressed in breast cancer cell lines and in cancer cells of some breast carcinomas but not in any non‐cancerous tissues examined, except skin. Another S100 gene, S100C, which we co‐localized with the psoriasin gene to human chromosome Iq21‐q22, was found to be expressed in most tissues and cell lines evaluated. These findings add support to the concept that the S100 genes clustered in human chromosome Iq21‐q22 are individually controlled and that some of them may be involved in the regulation of cell transformation and/or differentiation.
Deprivation, stage at diagnosis and cancer survival
Authors: Schrijvers Carola T. M. , Mackenbach Johan P. , Lutz Jean‐Michel , Quinn Michael J. , Coleman Michel P.
Published: February 2007

The association between an area‐based measure of deprivation and survival from the 10 most common cancers was studied in 155,682 patients diagnosed between 1980 and 1989 in the area covered by the South Thames Regional Health Authority. Furthermore, the impact of stage of disease at diagnosis on this association was studied. The measure of deprivation was the Car‐stairs Index of the census enumeration district of each patient's residence at diagnosis (5 categories) and the cancers studied were: lung, breast, colorectum, bladder, prostate, stomach, pancreas, ovary, uterus and cervix. In the univariate analyses the measure of outcome was the relative survival rate and in the multivariate analyses it was the hazard ratio. Both univariate and multivariate analyses showed that patients from affluent areas had better survival than patients from deprived areas for cancers of the lung, breast, colorectum, bladder, prostate, uterus and cervix. Stage of disease at diagnosis did not explain the survival differences by deprivation category. For cancers of the stomach, pancreas and ovary, no variation in survival by deprivation category was found. For most cancer sites, a clear gradient in survival by deprivation category was observed, which implies a large potential reduction of cancer mortality among the lower socioeconomic groups. Future studies need to incorporate other possible explanatory factors, besides stage, of the association between deprivation and survival.
Prognostic value of DNA index, S‐phase fraction and p53 protein accumulation after surgical resection of esophageal squamous‐cell carcinomas in Thailand
Authors: Chanvitan Apinop , Nekarda Hjalmar , Casson Alan G.
Published: February 2007

The prognostic value of cell nuclear DNA content, S‐phase fraction and p53 protein accumulation in esophageal squamous‐cell carcinomas was studied in a consecutive series of 80 patients from a high‐incidence region of southern Thailand, who underwent esophagectomy between 1983 and 1993. Flow cytometry was used to determine tumor ploidy, DNA index and S‐phase fraction, while p53 protein accumulation was evaluated immunohistochemically using the monoclonal anti‐p53 antibody, CO7. Biomarkers were correlated with clinico‐pathologic findings and survival by univariate and multivariate analysis. p53 protein was found in 40 tumors (50%), and was associated with significantly reduced overall survival. In patients with immunopositive tumors, depth of primary tumor invasion, lymph‐node status, TNM stage and tumor grade were also significant prognostic factors. Additional predictors of reduced overall survival after esophagectomy, determined by flow cytometry, included S‐phase fraction above 10%, aneuploidy (DNA index 1.2–1.8) and multiploidy (DNA index >2.2). This study further implicates p53 in the pathogenesis of esophageal squamous‐cell carcinoma. Prognostic factors such as p53 protein, S‐phase fraction and DNA index may be useful in stratifying patients for adjuvant therapies in future clinical trials of esophageal cancer.
Liver endothelial cells participate in T‐cell‐dependent host resistance to lymphoma metastasis by production of nitric oxide in vivo
Authors: Rocha Marian , Krüger Achim , Van Rooijen Nico , Schirrmacher Volker , Umansky Victor
Published: February 2007

Tumor growth and metastasis of IacZ‐transduced murine lymphoma ESbL cells inoculated into syngeneic DBA/2 mice are characterized by a transient plateau phase with a constant tumor diameter and low metastatic load, indicating a host response against the tumor. Here we show that endothelial cells participate in a T‐cell‐dependent, anti‐metastatic response by producing NO in situ. Liver endothelial cells were isolated and examined directly ex vivo without further manipulation. NO production in liver endothelial cells reached the highest level during the plateau phase but declined toward the end of it, followed by an overall breakdown of host response, leading to progressive tumor growth and high load of liver metastasis. Mice subjected to anti‐tumor immunization and subsequent challenge with a tumorigenic dose of ESbL‐IacZ cells showed, in comparison to non‐immunized challenged controls, reduced liver metastasis and increased endothelial NO production. Adoptive transfer of anti‐tumor immune spleen cells from semi‐allogeneic B10.D2 mice into tumor‐bearing animals during the plateau phase caused a regression of primary tumor and metastases, together with a preservation of the high level of NO synthesis in endothelial cells. In immuno‐incompetent (SCID) mice, tumor growth and metastasis were progressive and there was no endothelial NO response. Pre‐immunization of immuno‐competent mice with both live and irradiated tumor cells at different sites of the body led to an induction of NO production by liver endothelial cells. These results reveal a novel role of endothelial cells in the suppression of lymphoma metastasis in the liver. The inducible endothelial cell NO response is apparently dependent and induced by mature T lymphocytes.
Tenascin and fibronectin isoforms in human renal cell carcinomas, renal cell carcinoma cell lines and xenografts in nude mice
Authors: Lorn Jouni , Tani Taneli , Laitinen Liisa , Kangas Lauri , Lehto Veli‐Pekka , Virtanen Ismo
Published: February 2007

We studied the expression of tenascin (Tn) and isoforms of fibronectin (Fn) in human renal cell carcinomas (RCC) and oncocytomas, in RCC cell lines and in their s.c. implanted xenografts in nude mice. In well‐differentiated RCCs and oncocytomas extra‐domain A (EDA)‐Fn and Tn immunoreactivities were confined to the basement membranes and blood vessels, while in less‐differentiated RCCs they were also widely seen in the stroma, correlating with the morphological differentiation of the tumor. Expression of EDB‐Fn and oncofetal (onc)‐Fn was very scarce in most of the RCCs and oncocytomas. Western blotting results demonstrated the predominance of the Mr 190,000 Tn subunit in most RCCs. Among the 4 RCC cell lines, 3 showed Tn in the extracellular matrix. As xenografts, they formed moderately or poorly differentiated tumors, with abundant Tn. Three of the RCC cell lines also showed secretion of EDA‐Fn and 2 of them secretion of onc‐Fn and EDB‐Fn into the culture medium, while in xenografts there was a strong expression of all Fn isoforms. In xenografts, the expression of Tn closely recapitulated that seen in clinical tumors and in the cell lines in vitro, while the expression of Fn isoforms in cultured cells and their xenografts was highly discordant.
Hyaluronic acid/CD44H interaction induces cell detachment and stimulates migration and invasion of human glioma cells in vitro
Authors: Koochekpour Shahriar , Pilkington Geoffrey J. , Merzak Abderrahim
Published: February 2007

The mechanisms underlying the invasive properties of glio‐mas, the major form of intrinsic brain tumours in humans, are poorly understood. We have reported that CD44 plays an important role in this behaviour in vitro. In the present work, we investigated the role of its ligand, hyaluronic acid (HA), in invasion in 8 human glioma cell lines. We found that HA mediates cell detachment via its interaction with its high affinity receptor, CD44H. Using 8 μm porosity polycarbonate filter transwells, we demonstrate that HA strongly stimulates migration in all 8 cell lines. This effect was found to be partially counteracted by a CD44H monoclonal antibody (MAb), suggesting the involvement of CD44H, as well as other HA receptors, in this process. Furthermore, incorporation of increasing concentrations of HA in Matrigel in an in vitro invasion assay resulted in a substantial increase in the invasive propensity of the glioma cell lines. Moreover, blocking experiments with the CD44H MAb suggest that CD44H and other receptors interact with HA to promote cell invasion in vitro. Our results show that HA induces cell detachment, stimulates migration and promotes invasion via its interaction with CD44H and other HA receptors in vrtro. These effects could be prevented by use of specific HA receptor antibodies.
Inhibition of metastasis of lewis lung carcinoma by urinary trypsin inhibitor in experimental and spontaneous metastasis models
Authors: Kobayashi Hiroshi , Shinohara Hiromitsu , Fujie Michio , Gotoh Junko , Itoh Mariko , Takeuchi Kinya , Terao Toshihiko
Published: February 2007

A purified human urinary trypsin inhibitor (UTI) and its related synthetic peptides were examined to determine whether they could inhibit production of experimental and spontaneous lung metastases by murine Lewis lung carcinoma (3LL) cells. Three peptides, peptide 1, peptide 2 and peptide 3, representing the amino acid sequences within the UTI molecule, were synthesized. UTI and peptide 2 inhibited human leukocyte elastase (HLE). UTI and peptide 3 specifically inhibited human and murine plasmin activity. Peptide 1 had essentially no inhibitory activity. In an in vivo spontaneous metastasis model, multiple s.c. injections of UTI or peptide 3 for 7 days immediately after s.c. tumor cell inoculation significantly inhibited the formation of lung metastasis in CS7BL/6 mice in a dose‐dependent manner. UTI reduced lung tumor colonization more effectively than peptide 3. Peptides 1 and 2, however, did not affect the formation of lung metastasis. Inhibition of lung metastasis was not due to direct anti‐tumor effects of UTI and peptide 3. In an in vivo experimental metastasis assay, multiple s.c. injections of UTI for 7 days after i.v. tumor cell inoculation inhibited metastatic lung tumor colonization, while peptide 3 did not affect metastasis. Peptides 1 and 2 did not affect the formation of lung metastasis. When examined with an in vitro assay system using a modified Boyden chamber, UTI and peptide 3 suppressed the invasion of tumor cells through Matrigel. UTI and peptide 3 inhibited neither cell proliferation nor the binding of tumor cells to Matrigel and showed no significant suppression of chemotactic migration of tumor cells to fibronectin. Our results suggest that UTI efficiently regulates the mechanism involved in not only the entry into vascular circulation of tumor cells (intravasation, though, at least in part, inhibition of the proteolytic enzyme plasmin) but also the extravasation step of the metastatic process.
Epstein barr virus (EBV)‐carrying cells of a chronic lymphocytic leukemia (CLL) subpopulation express EBNA1 and LMPS but not EBNA2 in vivo
Authors: Laytragoon‐Lewin Nongnit , Chen Fu , Avila‐Cariño Javier , Zou Jie‐Zhi , Mellstedt Håkan , Ernberg Ingemar , Klein George
Published: February 2007

We have previously described an exceptional CLL patient, P.G., whose leukemic cell population contained a small fraction of Epstein‐Barr virus (EBV)‐carrying cells. These cells grow directly into permanent cell lines in vitro. Using RT‐PCR analysis, we now show that the in vivo EBV‐carrying CLL cells expressed EBNAI, LMPI, LMP2a and 2b, but not EBNA2, in 4 of 4 blood samples obtained during the last 3 years of the patient's life. Our data also show that the CLL cells used a promoter in the F/Q, but not the W or C, region. This is consistent with the fact that CLL cells resemble resting lymphocytes rather than immunoblasts. Expression of LMPI and LMP2b differs from the exclusive EBNAI and LMP2a expression of normal resting B cells, however, and corresponds to the state defined as latency II. This form of latency was until now detected only in EBV‐carrying non‐B cells in vivo. Our data show that a B‐cell subtype can also show this expression pattern in vivo.
A cohort study of serum testosterone and hepatocellular carcinoma in Shanghai, China
Authors: Yuan Jian‐Min , Ross Ronald K. , Stanczyk Frank Z. , Govindarajan Sugantha , Gao Yu‐Tang , Henderson Brian E. , Yu Mimi C.
Published: February 2007

Ahdnested case‐control study of HCC based on a cohort of 18,244 middle‐aged men in Shanghai, Chinahd who had been followed for an average of 5.3 years, was conducted. Our hypothesis dealt with the possible role of testosterone in the etiology of HCC, which shows a minimum of a 2‐ to 3‐fold male excess in all populations world‐wide. Seventy‐six incident cases of HCC and 410 control subjects drawn from the cohort and individually matched to the cases by age (within 1 year), time of blood sample collection (within 1 month) and neighborhood of residence were assessed for serum HBsAg, anti‐HBc, anti‐HBs, anti‐HCV and testosterone. Among controls, serum testosterone levels were similar between those who had no markers of HBV infection, those who were positive for anti‐HBs only and those who were positive for anti‐HBc but negative for HBsAg. However, the geometric mean level of testosterone in HBsAg‐positive controls was 21% higher relative to HBsAg‐negative controls and the difference was statistically significant (2‐sided p = 0.0006). Relative to controls, HCC cases had a significantly higher mean level of testosterone at the time of recruitment (570 vs. 485 ng/dl, 2‐sided p = 0.0005), but the difference was explicable on the basis of a higher proportion of HBsAg‐positive individuals among cases than controls (p = 0.42 after adjustment for HBsAg status).
Human papillomavirus type 18 DNA in gestational trophoblastic tissues and choriocarcinomas
Authors: Pao Chia C. , Hor Jyu Jen , Wu Chi‐Jung , Shi Yi‐Fu , Xm Xing , Lu Shi‐Ming
Published: February 2007

Thde objectives of our study were to better understand carcinogenesis of gestational trophoblastihd tumors and to investigate the possible presence of human papillomavirus types 16 and 18 DNA sequences in these tumors. Amplification‐based DNA methodology was used on 11 hydatidiform moles, 5 invasive moles, 8 choriocarcinomas and 9 normal early placental tissues. Human papillomavirus type 16 DNA was not found in any of these tissues. Although human papillomavirus type 18 DNA was also not found in the 9 normal placentas and 5 invasive moles, it was present in 2 of the 11 (18%) hydatidiform moles and in 4 of the 8 (50%) choriocarcinomas.
Expression and function of α2,3‐sialyl‐ and α,3/l,4‐fucosyltransferases in colon adenocarcinoma cell lines: Role in synthesis of E‐selectin counter‐receptors
Authors: Majuri Marja‐Leena , Niemelä Ritva , Tiisala Sinikka , Renkonen Ossi , Renkonen Risto
Published: February 2007

We show here that colon‐carcinoma cell lines adhere to E‐selectin via sialyl Lewis x and sialyl Lewis a (sLex and sLea) oligosaccharides and that this adhesion can be enhanced by TNF stimulation. To study in greater detail this endothelial binding, we analysed the mRNA expression and function of the enzymes participating in the generation of sLex and sLea on cancer cells. These oligosaccharides are synthesized by sequential action of α2,3 sialyl (α2,3‐ST) and α1,3/1,4 fucosyltransferases (α1,3/1,4‐FT) on existing (poly)N‐acetyllactosamine chains. We report here that mRNAs of 2 recently cloned α2,3‐STs and 4 α1,3/l,4‐FTs are expressed in adenocarcinoma cells. In functional assays α2,3‐ST and α1,3‐ or 1,4‐FT activities were observed in adenocarcinoma cell lysates to exogenous N‐acetyllactosamine and lacto‐N‐biose acceptors and to their sialytated derivatives, leading to the synthesis of the sialyl‐N‐acetyllactosamine and sLex or the sialyllacto‐N‐biose and sLea, respectively. Furthermore, the inflammatory cytokine TNF could enhance some α2,3‐ST and α1,3/1,4‐FT activities capable of generating E‐selectin counter‐receptors. Taken together, these data show that COLO 205 and HT‐29 adenocarcinoma cell lines adhere to E‐selectin in a TNF‐inducible manner via their cell‐surface sLex and sLea. These cells also express mRNA as well as inducible enzyme activities of several α2,3‐STs and α,3/1,4‐FTs responsible for the final steps in the synthesis of sLex and sLea. We show here that the TNF‐induced adhesion to E‐selectin might be due to the increased synthesis of sLex and sLea in colon‐carcinoma cells.
Marked acceleration of the metastatic phenotype of a rat bladder carcinoma cell line by the expression of human gelatinase a
Authors: Kawamata Hitoshi , Kameyama Shuji , Kawai Koji , Tanaka Yoshinori , Nan Li , Barch David H. , Stetler‐Stevenson William G. , Oyasu Ryoichi
Published: February 2007

Nhdmerous studies have reported a correlation between the production of gelatinases A and B by cancer cells anhd invasive and metastatic potential. It has been suggested that the expression of gelatinase A (72‐kDa type IV collagenase) is associated more closely with the metastatic phenotype of malignant cells in vitro and in vivo than that of gelatinase B (92‐kDa type IV collagenase). We have established a rat bladder carcinoma cell line, MYU3L, which is tumorigenic and locally invasive but is not metastatic to the distal organs in nude mice. The MYU3L cell line secretes pro‐gelatinase B but not any detectable level of pro‐gelatinase A. We undertook the present study to determine whether over‐expression of gelatinase A can affect the metastatic potential of MYU3L cells. We transfected MYU3L cells with an expression vector containing human pro‐gelotinase A cDNA under the transcriptional control of the SRα promoter. Two stable transfectants over‐expressing gelatinase A activity were isolated. We assessed the biological behavior of the transfectants by an orthotopic site (urinary bladder) inoculation and an i.v. injection in nude mice. Our results demonstrate that the induced expression of human gelatinase A enzyme markedly accelerates the metastatic phenotype of the rat bladder carcinoma cell Vine MYU3L. Our results suggest that gelatinase A produced by tumor cells plays a major role in the metastatic process.
Reaction of peripheral‐blood lymphocytes to the human chorionic gonadotropin β sub‐unit in patients with productive tumors
Authors: Housseau Frank , Rouas‐Freiss Nathalie , Benifla Jean‐Louis , Marcillac Isabelle , Roy Maguy , Troalen Frédéric , Fernandez Hervé , Prapotnich Dominique , Valencien Guy , Bougaran Joelle , Cottu Paul , Culine Stéphane , Droz Jean‐Pierre , Bidart Jean‐Michel , Bellet Dominique
Published: February 2007

Human chorionic gonadotropin (hCG) and its β sub‐unit (hCGβ) are secreted by trophoblast cells during pregnancy, and by tumoral cells of trophoblastic and non‐trophoblastic origin. In contrast to hCG, the free hCGβ sub‐unit is consistently undetectable in healthy non‐pregnant subjects. With this in mind, we sought to determine whether an immune response to hCGβ can be detected in patients with bladder or germ‐cell testis cancers. Peripheral‐blood mononuclear cells (PBMC) from 31% of patients with hCGβ‐productive bladder cancers and 33% of testis‐tumor‐bearing patients displayed an hCGβ‐specific proliferative response, whereas no patients with non‐hCGβ‐productive cancers had a proliferative response. PBMC from pregnant women and healthy controls did not elicit significant reactivity. By the use of overlapping synthetic peptides, the immunogenic regions of hCGβ were delineated within the central 20–65 portion. Moreover, in 2 bladder‐cancer patients with the HLA DR7, DQ2 haplotype, the T‐cell response to hCGβ was focused on the hCGβ(20–47) peptide. Taken together, these results indicate that hCGβ is a tumor‐associated antigen capable of inducing a cell‐mediated immune response in patients with productive tumors. © 1995 Wiley‐Liss, Inc.
Presence and persistence of HPV infection and p53 mutation in cancer of the cervix uteri and the vulva
Authors: Milde‐Langosch Karin , Albrecht Kathrin , Joram Simone , Schlechte Horst , Giessing Markus , Löning Thomas
Published: February 2007

We studied 51 cervical carcinomas, among them 25 squamous‐cell carcinomas (SCC) and 26 cervical adenocarcinomas (AdCa), and 40 vulvar SCC for the presence of HPV and mutant p53. HPV was detected by PCR, and p53 alterations by temperature‐gradient gel electrophoresis/direct sequencing and immunohistochemistry. HPV, mostly type 16/18, was found in 80.4% of the cervical tumors (92.0% of the SCC and 69.2% of the AdCa), but in only 27.5% of vulvar carcinomas. In contrast, p53 mutations were found in 7.8% and 52.5% of cervical and vulvar tumors respectively. Mutant p53 occurred in pre‐invasive vulvar lesions, indicating that this oncogenic factor is involved early in carcino‐genesis. Further analysis of recurrent/metastatic lesions of 9 cervical and 14 vulvar tumors also showed remarkable differences: in cervical cancer, HPV was persistent, and p53 mutations absent, whereas in vulvar tumors, HPV was mostly absent or not persistent, and the p53 mutation rate was very high (78.6%). These observations suggest that HPV persistence is an important event for the evolution and maintenance of cervical cancer, whereas for vulvar cancers p53 mutation and not HPV activity is a central oncogenic event. © 1995 Wiley‐Liss, Inc.