bluuebunny/crossref_metadata_2025 huggingface dataset:
Target lysis by human lak cells is critically dependent upon target binding properties, but LFA‐1, LFA‐3 AND ICAM‐1 are not the major adhesion ligands on targets
Authors: Quillet‐Mary Anne , Cavarec Laurent , Kermarrec Nathalie , Marchiol‐Fournigault Carmen , Gil Maria Luisa , Conjeaud Hélène , Fradelizi Didier
Published: February 2007

The cytotoxicity mediated by the CD2+ CD3− lymphocyte subset, either NK or LAK, is puzzling since no specific antigen recognition structures, equivalent to the CD3− associated het‐erodimer T‐cell receptor, have been recognized on these cells so far. The possibility exists that the CD3− cytotoxic effectors recognize their targets through non‐specific adhesion mechanisms. The goal of this study was: (a) to examine the correlation between binding properties and susceptibility to lysis of 6 informative target cell lines; (b) to evaluate the role, as ligands on these targets, of adhesion molecules such as LFA‐I, LFA‐3 and ICAM‐I. The effectors used in this study were IL‐2‐activated LGL, predominantly CD3, or highly purified CD3− lymphocytes from normal human donors. The 6 target lines studied included 2 pairs of EBV‐transformed B‐cell lines (721 LCL vs. 721.134, and MM vs. MM‐10F2) in which the parental lines were resistant to lysis while HLA variants were susceptible. A third pair was the Daudi Burkitt cell line, susceptible to LAK lysis, and an HLA‐positive transfected Daudi line which was more resistant to lysis. The binding properties of these targets to LAK effectors (conjugate formation) were evaluated using a sensitive double fluorescence flow cytometry method. In each pair examined, the susceptible targets formed more conjugates and were surrounded by more cytotoxic LAK effectors than their resistant counterparts, indicating that the conjugation properties of targets are closely correlated with their susceptibility to LAK lysis. The expression of adhesion molecules on the informative targets was examined by indirect immunofluorescence and their role was evaluated by inhibition of lysis after pre‐coating the targets with the relevant antibodies. The differences in the expression of the classical cell‐cell adhesion molecules LFA‐1, LFA‐3 and ICAM‐1 on the target surfaces were only marginal, insufficient to explain the striking differences in susceptibility to lysis and in binding properties. Coating the target cells with antibodies directed against these adhesion determinants had no effects on the lysis of susceptible target cells. The same antibodies reacting with the LAK effectors did inhibit lysis. Taken together, these results suggest that, on the targets, presently undefined membrane adhesion structures may have a major role in conjugate formation between target and CD3 effectors and determine the susceptibility of the targets to lysis.
Temporal change in diagnostic criteria as a cause of the increase of malignant melanoma over time is unlikely
Authors: Van Deresch E. P. , Muir C. S. , Nectoux J. , Macfarlane G. , Maisonneuve P. , Bharucha H. , Briggs J. , Cooke R. A. , Dempster A. G. , Essex W. B. , Hofer P. A. , Hood A. F. , Ironside P. , Larsen T. E. , Little J. H. , Philipps R. , Pfau R. S. , Prade M. , Pozharisski K. M. , Rilke F. , Schafler K.
Published: February 2007

To assess whether the increase in malignant melanoma incidence could be due, at least in part, to changes in histological criteria of malignancy, pathologists in Australia, France, Italy, New Zealand, Norway, Sweden, the United Kingdom, the United States and the USSR reviewed diagnoses of 50 consecutive pigmented naevi (40 junctional and compound; 10 intradermal) and 20 consecutive malignant melanomas made in each participating centre around 1930, around 1955 and around 1980. Collaborating pathologists re‐read the material, 2,665 cases in all, either from the original slide (82%) or from a recut block (17%), gave their diagnosis and indicated whether the lesion was benign (B), dubious benign (DB), dubious malignant (DM) or malignant (M). As the distribution of review diagnoses was much the same whether the original slide or one made from a recut block was read, the material was pooled. Overall, 2.8% of cases originally reported as B/DB were reviewed as DM/M, while 4.4% of the DM/M diagnoses were held to be B/DB. The shifts between categories were greatest around 1955 and least around 1980, suggesting increasing uniformity of interpretation. All available blocks were recut and sections sent to I ARC for review: 1.7% (22) of 1293 B/DB diagnoses were considered to be DM/M and 3.3% (18) of 551 DM/M diagnoses were considered to have been B/DB. The consistently low frequency of shift in diagnostic category, whether the material was reviewed in the collaborating laboratories or by one pathologist at IARC, in a study designed to give maximum attention to those lesions‐the junctional and compound naevi‐in which a change in opinion as to malignancy would be most likely to arise, suggests that pathologists, irrespective of geographical location, are using common criteria. These findings argue against changes in histological interpretation as being responsible for more than a small portion of the continuous increase of some 3% to 8% per annum observed in malignant melanoma incidence. Other explanations, such as an increase in the frequency or potential for malignant transformation of precursor lesions, must be sought. The anatomical distribution of the malignant melanomas examined followed the usual site pattern by sex, and their thickness was observed to decrease over the period of the study in most centres.
EGF in breast cyst fluid: Relationships with intracystic androgens, estradiol and progesterone
Authors: Boccardo F. , Torrisi R. , Zanardi S. , Valenti G. , Pensa F. , De Franchis V. , Barreca A. , Ferraro P. , Minuto F.
Published: February 2007

The relationship between intracystic levels of epidermal growth factor (EGF) and those of dehydroepiandrosterone sulphate (DHEA‐S), Δ‐4‐androstenedione (Δ‐4‐A), 17‐β‐estradiol (17‐β‐E) and progesterone (PROG) have been studied in 77 breast cyst fluid (BCF) samples. EGF and all tested hormones appeared to be inversely correlated with the intracystic Na+/K+ ratio (p < 0.001). Consequently, when the BCFs were subdivided according to the Na+/K+ ratio, significantly higher levels of EGF, DHEA‐S, Δ‐4‐A, 17‐β‐E and PROG were found in Na+/K+ < 3 BCFs compared with Na+/K+ > 3 BCFs (p< 0.001 in all cases). Strong direct relationships were found among all steroid hormones when they were correlated to one another (p< 0.001). Intracystic EGF concentration was directly and significantly correlated with each tested hormone (p< 0.001). However, the relationship between EGF and steroid hormones appeared to be different in the 2 BCF types (Na+/K+ < 3 or >3).
Characterization by somatic cell genetics of a monoclonal antibody to the MDR1 gene product (P‐glycoprotein): Determination of p‐glycoprotein expression in multi‐drug‐resistant kb and cem cell variants
Authors: Cenciarelli Cristina , Currier Stephen J. , Willingham Mark C. , Thiebaut Franz , Germann Ursula A. , Rutherford Angelina V. , Gottesman Michael M. , Barca Stefano , Tombesi Marina , Morrone Stefania , Santoni Angela , Mariani Massimo , Ramoni Carlo , Dupuis Maria Luisa , Cianfriglia Maurizio
Published: February 2007

We isolated an IgG2a murine monoclonal antibody (MAb) termed MAb57, specifically reactive with multi‐drug‐resistant (MDR) human cells. Its specificity toward the MDRI gene product (P‐glycoprotein) has been demonstrated by the concordant segregation of the MAb57 epitope with the MDRI gene in interspecific mouse × human cell hybrids, and the reactivity of several different MDRI gene‐expressing cells with Mab57, particularly insect cells acutely infected with a baculovirus encoding the MDRI gene. Mab57 can be used to detect, by flow cytometry, variations in the relative drug‐resistance levels of several MDR KB and CEM cell variants. This immunological probe has also proven useful in selectively destroying MDR target cells in an antibody‐dependent cell‐mediated (ADCC) assay system as well as in detecting P‐glycoprotein expression in normal and malignant tissues and cells.
aberrant expression of HLA Class‐I antigens in burkitt lymphoma cells
Authors: Andersson Monika L. , Stam Nico J. , Klein George , Ploegh Hidde L. , Masucci Maria G.
Published: February 2007

HLA class‐1 expression has been investigated by biochemical methods in 14 Burkitt lymphoma (BL) cell lines and the corresponding Epstein‐Barr virus (EBV)‐transformed lymphoblastoid cell lines (LCL) derived from the same individuals. Selective down‐regulation of one or more HLA class‐1 specificities was demonstrated in 9 out of 14 BL lines. The defect was restricted to a single HLA‐A allele in 3 of the lines (BL29, BL72, WW‐1‐BL). Four lines (BL28, BL37, BL41 and Jijoye M13) showed down‐regulation of both HLA‐A and ‐C alleles, and one (BL36) failed to express one HLA‐C allele. Only one BL line (WW‐2‐BL) had lost one HLA‐A and one HLA‐B allele. The allele‐specific defects were mainly detected in cell lines that had maintained the phenotypic characteristics of the original tumor. Expression of B‐cell activation markers and the EBV‐encoded nuclear antigen (EBNA)‐2 correlated with up‐regulation of the Cw4 allele in the P79 subline of the BL line Jijoye. Treatment with gamma‐interferon (IFN) resulted in full or partial reversion of the HLA class‐1 defects in some of the cases but had no significant effect in others. This was not due to a cell‐line‐related unresponsiveness to IFN, nor did it reflect an allele‐specific mode of regulation because the same allele could respond differently in different cell lines. The data suggest that defective expression of HLA class‐1 antigens, which appears to be more prevalent for alleles within the HLA‐A and ‐C loci, is a common feature of BL cell lines. Different regulatory mechanisms appear to be involved.
Heterogeneity for integrin expression and cytokine‐mediated VLA modulation can influence the adhesion of human melanoma cells to extracellular matrix proteins
Authors: Mortarini Roberta , Anichini Andrea , Parmiani Giorgio
Published: February 2007

Expression of α and β subunits of VLA and VNR integrins was analyzed by cytofluorimetric analysis on 6 different human primary and metastatic melanoma cell cultures. Marked inter‐tumor heterogeneity was observed, and expression of VLA‐α, VLA‐α2 and VLA‐α6 was lower on primary melanomas than on metastatic lesions. The function of VLA products on melanoma cells was assessed by adhesion assays to extracellular matrix (ECM) proteins using a panel of melanoma clones previously characterized for the presence and heterogeneity of expression of the distinct VLA‐α subunits. These experiments indicated that intra‐tumor heterogeneity in the integrin profile can influence the interaction of neoplastic cells with ECM proteins. Inhibition of adhesion with antibodies to VLA‐α subunits revealed that the presence on melanoma cells of VLA‐α2, VLA‐α5 and VLA‐α6 is relevant for the adhesion to type‐IV collagen, fibronectin and laminin respectively. Culture of tumor cells in the presence of cytokines such as rIL‐1β, rTNF‐α, rIFN‐γ or TGF‐β could induce up‐ or down‐modulation in the level of expression of multiple VLA integrins. Cytokine‐mediated antigenic shifts in the VLA profile of melanoma cells were detected by cytofluorimetric analysis as early as 24 hr after cytokine exposure. The cytokine‐dependent change in the matrix receptor profile of melanoma cells also affected the adhesion to ECM proteins as revealed by the enhanced adhesion of rTNF‐α‐treated cells to fibronectin. These data indicate that constitutive heterogeneity in the integrin profile or cytokine‐mediated shifts in VLA expression can affect the ability of human melanoma cells to interact with different ECM components.
Invasion of rous sarcoma virus‐transformed retinal cells: Role of cell motility
Authors: Brady‐Kalnay Susann M. , Soll David R. , Brackenbury Robert
Published: February 2007

Transformation of retinal neuro‐epithelial cells by Rous sarcoma virus (RSV) leads to many alterations in cell phenotype, including changes in cell movement, cell‐cell adhesion and protease secretion. To define and quantitate the alterations in cell movement, we analyzed video recordings of cultured cells using the computer‐assisted Dynamic Morphology System (DMS). Control neuro‐epithelial cells showed very low levels of translocation and membrane activity. After transformation, neuro‐epithelial cells exhibited increased membrane activity, although directed cell translocation remained low. Developing retinas also contain a small proportion of Muller glial cells, which were purified by repeated passaging of control cultures. In contrast to neuro‐epithelial cells, both control and RSV‐transformed glial cells showed high levels of translocation and membrane activity. To analyze how different kinds of cell movement affect invasive behavior, we compared the ability of control and RSV‐transformed cells to invade the chorio‐allantoic membrane of developing chicken embryos. Control neuro‐epithelial cells were not invasive. RSV‐transformed neuro‐epithelial cells, which showed low levels of translocation as revealed by DMS, were invasive. Similarly, RSV‐transformed glial cells were invasive while control glial cells, which translocated, were not invasive. These results suggest that high levels of cell translocation are not necessary for invasion. In addition, the results suggest that elevated membrane activity in neuro‐epithelial cells may be important for their invasion.
Immunotherapy of a mouse mammary carcinoma by sustained peritumor release of IL‐2
Authors: Vaage Jan , Mayhew Eric
Published: February 2007

The purpose of this study was to compare the local and systemic therapeutic effects of lnterleukin‐2 (IL‐2) used in 3 different preparations: suspended in PBS, suspended in 2% agar, and entrapped in multi‐lamellar liposomes suspended in 2% agar. The liposomes were composed of phosphatidylglycerol and phosphatidylcholine in a 1:4 molar ratio. The net release of IL‐2 in vitro (by ELISA assay) at 37°C, measured at 4 hr, 2 days, and 10 days, was 50%, 75%, and 100% from agar, and 8%, 22%, and 33% from liposomes in agar. In the therapeutic tests, the IL‐2 preparations were injected close to s. c. implants of the MC2 mouse mammary carcinoma. Four injections at weekly intervals of IL‐2 in agar had as much local and systemic (against uninjected contralateral tumor implants in treated mice) therapeutic effect as the same total amount of IL‐2 in PBS given in 20 daily injections over 4 weeks. The IL‐2 liposome‐gel preparation was most effective (p < 0.05), probably due to the more sustained release of IL‐2. Three injections of this preparation gave a fixed and sustained peritumor release of IL‐2 which, at sub‐toxic levels, resulted in both local and systemic therapeutic effects.
Human colon carcinoma, fibrosarcoma and leukemia cell lines produce tumor‐associated trypsinogen
Authors: Koivunen Erkki , Saksela Olli , Itkonen Outi , Osman Sirpa , Huhtala Marja‐Liisa , Stenman Ulf‐Håkan
Published: February 2007

Previous studies have indicated that cyst fluid of ovarian tumors contains 2 trypsinogen isoenzymes, called tumor‐associated trypsinogen‐1 (TAT‐1) and trypsinogen‐2 (TAT‐2), the levels of which correlate with the degree of malignancy of the tumors. In addition, these cyst fluids contain large amounts of tumor‐associated trypsin inhibitor (TATI), which is also expressed in many other human tumors. In the present study we examined the production of TAT‐1, TAT‐2 and TATI in 9 established tumor‐cell lines. TAT‐2 was produced by 5 cell lines. Its concentration in the conditioned medium of COLO 205 colon adenocarcinoma cells, K‐562 erythroleukemia cells and fibrosarcoma cell lines HT 1080,8387 and A 9733 was 460 μg/1, 9.8 μg/1, 21 μg/1, 8.8 μg/1 and 0.24 μg/l, respectively. TAT‐1 was detectable in the conditioned medium of COLO 205 and HT 1080 cells at concentrations of 64 μg/1 and 0.5 μg/1, respectively. TATI was detected only in the media of COLO 205 cells at a concentration of 23 μg/1. TAT‐2 zymogen was purified from the conditioned medium of COLO 205 and HT 1080 cells by immunoaffinity chromatography. According to its aminoterminal amino acid sequence, a molecular mass of 28 kDa by SDS‐PAGE, elution pattern in ion‐exchange chromatography and ability to be activated by enteropeptidase, the zymogen is identical to that previously isolated from cyst fluid of ovarian tumors. In addition, we found that TAT‐2 secretion could be down‐regulated by dexamethasone in HT 1080 cells but not in COLO 205 cells. The abundant production of TAT‐2 isoenzyme in different cancer cell lines suggests that it could contribute to the increased proteolytic activity of many human tumors.
Inhibition of respiration of tumor cells by methylglyoxal and protection of inhibition by lactaldehyde
Authors: Ray Manju , Halder Jyotsnabaran , Dutta Samir K. , Ray Subhankar
Published: February 2007

The effect of methylglyoxal (MG), ascorbic acid and lactaldehyde has been tested on the in vitro respiration of Ehrlich ascites carcinoma (EAC) cells and several normal and malignant human tissues. Methylglyoxal inhibited the respiration of each type of malignant cell and tissue tested, but it had practically no inhibitory effect on the respiration of any of the normal cells and tissues. Ascorbic acid exhibited a synergistic effect with MG in inhibiting the respiration of all the neoplastic cells. In the presence of lactaldehyde, a catabolite of MG, the inhibitory effect of MG on the respiration of tumor cells was significantly reduced. Lactaldehyde can exert a similar protective effect on the loss of viability and transplantability of MG‐treated EAC cells.
The effect of dibutyryl camp (dBcAMP) on morphological differentiation, growth and invasion in vitro of a hamster brain‐tumor cell line: A comparative study of dBcAMP effects in 2‐ and 3‐dimensional cultures
Authors: Boghaert E. R. , Simpson J. , Jacob R. J. , Lacey T. , Walsh J. W. , Zimmer S. G.
Published: February 2007

The use of agents that stimulate cancer cells to differentiate is proposed as a potential approach to the treatment of malignancy. To evaluate the effects of a differentiation inducer on morphology, growth and invasion in vitro of brain‐tumor cells, a diffusely invasive hamster glial cell line (CxT3C15) was treated with Imm dibutyryl cyclic adenosine monophosphate (dBcAMP). The efficacy of dBcAMP was tested in monolayer cultures, 3‐dimensional static cultures (i.e., spheroids) and confrontation cultures with an embryonic chick heart. CxT3C15 cells exhibited increased numbers of long cellular processes (morphological differentiation) following treatment of monolayer cultures with Imm dBcAMP. One mm dBcAMP also altered the macroscopic and ultrastructural morphology of CxT3C15 grown as spheroids. These alterations were: (i) a fast transition of rough to smooth morphology macroscopically, and (ii) fading of the cell borders concomitant with the disappearance of cell‐membrane excrescences, as seen by scanning electron microscopy. Exponential growth of CxT3C15 in monolayers was not changed following treatment with ImM dBcAMP. Treatment of CxT3C15 spheroids with the same dose of dBcAMP caused a reduction of relative volume increase (30‐40%). Invasion of CxT3C15 in an embryonic chick heart in vitro was not altered after addition (prior to or at the time of co‐culture) of Imm dBcAMP to the co‐cultures.

These results indicate that invasion of CxT3C15 is not necessarily linked to morphological differentiation or moderated by reduced proliferation.
Characterization of a newly established human burkitt's lymphoma cell line, OMA‐BL‐1
Authors: Joshi Shantaram S. , Deboer Joanne M. , Strandjord Sarah J. , Pirruccello Samuel J. , Sanger Warren G. , Weisenburger Dennis D. , Sharp J. Graham
Published: February 2007

Using culture techniques, we have been able to grow occult tumor cells from the bone marrow from cancer patients and have developed a new malignant lymphoid cell line, OMA‐BL‐I, from the bone marrow of a 17‐year‐old patient with recurrent Burkitt's lymphoma. The tumor cells grew rapidly in vitro in suspension culture, and very aggressively in vivo in athymic nude mice with metastases to the liver and abdominal cavity. The morphological, chromosomal, immunophenotypic and molecular biologic characteristics of fresh uncultured tumor cells from the patient and tumor cells grown in culture and in athymic nude mice were very similar. The cells were positive for Epstein‐Barr virus‐associated nuclear antigens (EBNA) and chromosome analysis of the cells revealed an atypical chromosomal abnormality of 45, X, ‐X, i(8q), HSR(18)(q21), t(8;14)(q24;q32). Southern analysis demonstrated that c‐myc was rearranged and amplified in these cells. Immunophenotypic analysis of the cells using flow cytometry showed monoclonal B cells expressing a surface IgG‐kappa isotype. The tumor cells grown in nude mice had a significant decrease in CD24 expression when compared to cultured tumor cells. Electron microscopy of the fresh and cultured cells revealed Herpes virus, most likely Epstein‐Barr virus, particles. This cell line has been maintained in culture for over 18 months. The aggressive growth and metastatic properties of this cell line in athymic nude mice make it a potentially useful experimental model to study the biology of human lymphoma.
Activity of thymidylate synthetase, thymidine kinase and galactokinase in primary and xenografted human colorectal cancers in relation to their chromosomal patterns
Authors: Bardot V. , Luccioni C. , Lefrançois D. , Muleris M. , Dutrillaux B.
Published: February 2007

The relationship between chromosome anomalies and metabolic modifications in human colorectal cancers grafted into nude mice was studied. Two distinct chromosomal patterns have been demonstrated i.e., monosomic type (MT) characterized by multiple chromosome losses or deletions always involving chromosome 18, and trisomic type (TT) characterized by progressive gains of chromosomes. Grafted tumors conserve original karyotypes observed on corresponding primary tumors. Most changes involve the loss of chromosomes carrying genes encoding for enzymes of the de novo pathways and the gain of chromosomes carrying genes encoding for enzymes of the salvage pathways of nucleotide synthesis. In MT tumors the long arm (q) of chromosome 17 is frequently duplicated in association with a deletion of the short arm, forming an isochromosome 17q. The activities of 3 enzymes, thymidylate synthetase (TS) mapped on chromosome 18, thymidine kinase (TK) and galactokinase (GalK), both mapped on chromosome 17q, were studied. TS is a de novo enzyme and TK and GalK are salvage enzymes. A clear correlation could be demonstrated between tumor types and enzyme activities: MT tumors had lower TS and higher TK and GalK activities than TT tumors. These differences were too large to result from a gene dosage effect only. These data suggest that serial studies on grafted colorectal cancers give a better representation of metabolic disturbances than studies on fresh tumor samples, usually contaminated by non‐cancerous cells.
Detection of HPV DNA in neoplastic and non‐neoplastic cervical specimens from pakistan and japan by non‐isotopic in situ hybridization
Authors: Anwar Khurshid , Inuzuka Manabu , Shiraishi Taizo , Nakakuki Kazuya
Published: February 2007

In order to determine the prevalence and type‐specific distribution of human papillomavirus (HPV) in women from Pakistan, a country with a low cervical cancer rate (hospital‐based data), and to compare these results with their counterparts in Japan, we studied 56 non‐neoplastic cervical tissues and 162 cervical carcinoma cases from both countries. HPV infection was defined by in situ hybridization in paraffin‐embedded tissues using biotinylated HPV 6/11, 16 and 18 probes. The overall positivity rates in non‐neoplastic and neoplastic cervical tissues from Pakistan were 33% and 88%, while in those from Japan the rates were 46% and 80%, respectively. High‐risk HPVs (16 & 18) were found in 17% of the non‐neoplastic specimens and in 69% of cervical carcinoma cases from Pakistan, while Japanese figures in this respect were 19% and 68%, respectively. No correlation was found between the type‐specific distribution or prevalence of HPV and the geographic location of the cases examined in the 2 countries. However, in comparison to Japanese women, the incidence of HPV‐16‐positive cervical carcinoma in Pakistani women decreased significantly (p < 0.05) in the oldest age group as compared to the youngest age group.
Smoking and peripheral type of cancer are related to high levels of pulmonary cytochrome P450IA in lung cancer patients
Authors: Anttila Sisko , Hietanen Eino , Vainio Hard , Camus Anne‐Marie , Gelboin Harry V. , Park Sang S. , Heikkilä Lasse , Karjalainen Antti , Bartsch Helmut
Published: February 2007

A specific member of the cytochrome P450 super‐family of enzymes, designated P450IA (including 2 isozymes, P450IAI and P450IA2), which is involved in the metabolic activation of polycyciic aromatic hydrocarbons and aromatic amines, was studied in lung tissue from 25 lung cancer patients by immunohistochemistry. The pulmonary activity of a P450IAI‐dependent enzyme, aryl hydrocarbon hydroxylase (AHH), from the same patients was also measured. Cytochrome P4S0IA was localized principally in the peripheral airways in alveolar epithelium of types I and II and in ciliated columnar and cuboidal bronchiolar epithelium. The amount of P450IA in the bronchial wall was minimal and was localized mainly in the capillary endothelium and the epithelium of the bronchial glands. Smoking was the most important factor related to the presence of P450IA and the AHH activity in lung tissue. None of the 10 ex‐smokers, but all except I of the current smokers had detectable levels of P450IA. The localization of the cancer was also correlated with the presence of cytochrome P450IA. Peripheral lung tissue stained positively in all patients with a peripheral adenocarcinoma who currently smoked (8/8) but in less than half of those with a bronchial cancer who were smokers (3/7). Our data suggest that the smokers who have an inducible cytochrome P450IA are especially at increased risk of developing lung cancer of the peripheral adenocarcinomatous type.
Assessment of proliferative activity in carcinomas of the human alimentary tract by Ki‐67 immunostaining
Authors: Porschen Rainer , Kriegel Anja , Langen Christa , Classen Susanne , Hilse Martina , Lohe Bernd , Hengels Klaus‐Jürgen , Borchard Franz
Published: February 2007

The monoclonal antibody (MAb) Ki‐67, which is directed against a proliferation‐associated nuclear antigen, was used to measure tumor proliferation in 165 carcinomas of the esophagus, stomach, colon and rectum with an indirect immunoperoxidase technique. The percentage of Ki‐67‐positive tumor cells (Ki‐67 index) was evaluated with the point‐counting method. The Ki‐67 index in gastric cancers (mean, 24.8%; standard deviation, 11.1%) was significantly lower than in tumors of the esophagus (35.7 ± 12.6%), colon (37.6 ± 15.2%), and rectum (34.3 ± 16.4%). A wide range of the Ki‐67 index (5.9‐75.3%) could be observed within the various tumor types. In recurrent colorectal carcinomas, the Ki‐67 index significantly increased to 51.9%. The Ki‐67 index was independent of pathologic (e.g., TNM‐stage, grading, tumor volume, tumor site) and clinical variables (age and gender of the patients). A marked heterogeneity of Ki‐67 expression within different tumor stages was noted. Statistically significant regional variations in tumor proliferation existed between different areas within the same tumor.
Benign breast disease and breast cancer: A case‐control study in a cohort in italy
Authors: Palli Domenico , Turco Marco Rosselli Del , Simoncini Roberta , Bianchi Simonetta
Published: February 2007

Sixty‐two cases of invasive breast cancer were identified in a large cohort of women previously treated for biopsy‐proven benign breast disease (BBD) at the Breast Unit of CSPO, in Florence, along with a group of 315 controls, strictly matched by age and year of diagnosis. A pathologist reviewed and reclassified all the original BBD slides according to recently proposed criteria (no evidence of epithelial proliferation, epithelial proliferation without or with atypia). Information about potential confounding factors was collected during personal interviews. In comparison to the women with „non‐proliferative”︁ BBD, women classified as having „proliferative disease without atypia”︁ showed a weak and non‐significant increase in risk (OR 1.3; 95% CI: 0.5‐3.5). In contrast, women with „atypical hyperplasia”︁ were at very high risk of developing breast cancer (OR 13.0; 95% CI: 4.1‐41.7). When planning mammography screening or other large‐scale early‐diagnosis programmes for breast cancer in the general female population, follow‐up of high‐risk subgroups of BBD patients should be considered.
Human papillomavirus types 16 and 33, herpes simplex virus type 2 and other risk factors for cervical cancer in sichuan province, china
Authors: Peng Hongqi , Liu Shanling , Mann Valerie , Rohan Thomas , Rawls William
Published: February 2007

Cancer of the cervix is relatively common in China, but has been investigated epidemiologically in only a few studies. In the hospital‐based case‐control study reported here, we investigated the role of various lifestyle and dietary factors, as well as infection with human papillomavirus (HPV) types 16 and 33 and herpes simplex virus type 2 in the aetiology of invasive cervical cancer. The study was conducted in Sichuan province, and involved 101 cases with histologically‐confirmed cervical cancer recruited from the gynaecological oncology clinic of the West China University Hospital, and 146 controls recruited from patients attending the gynaecology clinic of the same hospital. Risk of cervical cancer was greatly increased in association with infection with HPV 16/33, the adjusted odds ratio for those with evidence of infection being 32.9 (95% Cl 7.7‐141.1). In contrast, infection with HSV 2 was not associated with a significantly altered risk of cervical cancer. Indices of sexual history and of dietary habits also showed no association with risk of cervical cancer, while good personal and genital hygiene were associated with markedly reduced risk. Although the results of this study are consistent with a causal role for HPV in the aetiology of cervical cancer, bias or increased viral expression following malignant transformation cannot be excluded as explanations for the strong positive association.
A novel prostate carcinoma‐associated glycoprotein complex (PAC) recognized by monoclonal antibody turp‐27
Authors: Wright George L. , Beckett Mary Lou , Lipford Grayson B. , Haley Cara L. , Schellhammer Paul F.
Published: February 2007

A prostate carcinoma‐associated antigen recognized by MAb TURP‐27 was characterized immunohistochemically and biochemically. TURP‐27 antigen was found localized in the cell membrane and cytoplasm of the ductal epithelial cells of normal (10%), benign (75‐100%) and malignant (20‐100%) prostate cells. Fetal prostate tissues were also found to express the TURP‐27 antigen, suggesting expression early in development. This antigen was not expressed by non‐prostate tumors examined, but significant cross‐reactivity was observed in myelinated nerves while minor cross‐reactivity was seen in certain lymphocyte subsets, cells in the adrenal medulla and chief cells of stomach. Immunoblotting and biochemical data demonstrated that the TURP‐27 antigen is a sialic‐acid‐containing glycoprotein complex with major molecular species in prostate tissues of 310‐250, 180, 140, 115, 95‐90,69, and 40‐ to 35‐kDa. Immunoblotting patterns similar to those observed for prostate tissues were also seen in CNS extracts with the exception of the 69 and 40‐ to 35‐kDa proteins. This prostate carcinoma‐associated sialoglycoprotein complex (PAC) recognized by MAb TURP‐27 is likely to represent a novel tumor antigen expressed by prostate tumors.
Inhibition by putrescine of experimental carcinogenesis in rat colon induced by azoxymethane
Authors: Tatsuta Masaharu , Iishi Hiroyasu , Baba Miyako , Ichii Makoto , Nakaizumi Akihiko , Uehara Hiroyuki , Taniguchi Haruo
Published: February 2007

The effects of putrescine on the incidence and number of colon tumors induced by azoxymethane, and on the labelling index and the activity of ornithine decarboxylase (ODC) in the colon mucosa were investigated in Wistar rats. Rats received 10 weekly injections of 7.4 mg/kg body weight of azoxymethane and i.p. injections of 300 μmol/kg body weight of putrescine every 2 days until the end of the experiment at week 40. This prolonged treatment with putrescine significantly reduced the incidence and number of colon tumors. Administration of putrescine also significantly decreased the labelling index and the ODC activity in the colon mucosa during, but not after, treatment with the carcinogen. These last effects may be related to the action of putrescine in inhibiting the development of colonic tumors.
Role of the extracellular matrix on the growth and differentiated phenotype of murine colonic adenocarcinoma cells in vitro
Authors: Walling Jackie M. , Blackmore Melanie , Hickman John A. , Townsend K. M. Stuart
Published: February 2007

The growth and differentiation characteristics of MAC 15 murine adenocarcinoma cells, derived from routine passage in vivo for growth in vitro on a plastic substrate (MACI5J cells), were compared under conditions in which the cells were seeded onto a substrate of type‐1 collagen which was either attached to plastic or was released to float free in medium. Cells grown on a plastic substrate consisted of a heterogeneous, largely anaplastic population with a putative en‐terocytic morphology but with no evidence of junctional complexes or cell polarity typical of an epithelial phenotype. MAC 15j cells from cultures grown on a plastic substrate reestablished a moderate to well‐defined degree of differentiation when transplanted back into NMRI mice. When MAC 15j cells were seeded from plastic onto type‐1 collagen, either attached to plastic or free‐floating, tight junctional complexes were formed and the cells began to attain a more recognizable, columnar and polarised epithelial morphology. Cells grown on a type‐1 collagen gel which was free‐floating showed a selective expression of alkaline phosphatase at the apical surfaces of approximately 10% of the cells. This expression was detectable by electron microscope histochemistry but could not be detected biochemically. Treatment of MAC 15j cells grown on a released collagen matrix with tetramethyl‐urea (20mM) accelerated the expression of alkaline phosphatase activity at the apical surface as detected by microscopy.
Urban and rural factors in the aetiology of cancer
Authors: Doll Richard
Published: February 2007

The incidence of cancer, or the mortality attributed to it, has been compared in urban and rural residents in 13 populations. In each case, the incidence (or mortality) has been higher in the urban areas in each sex, the ratios varying from a minimum of 1.03 to I in men in Japan to 1.63 to I in men in Denmark. Examination of 26 separate types of cancer showed that 23 tended to be more common in towns, I (myeloma) to be evenly distributed, and 2 (cancers of the lip and eye) to be more common in the countryside. The urban excess was greatest for cancers of the bladder, larynx, liver, lung, mouth and pharynx, and oesophagus, and least for leukaemia and non‐Hodgkin's lymphoma. It is concluded that differences in personal behaviour (cigarette smoking, alcohol consumption, sexual promiscuity, exposure to ultraviolet light, type of diet, and family size) are the principal factors responsible for the urban excess. Other factors include general atmospheric pollution, occupational hazards, genetic differences in susceptibility, and artefacts of diagnosis and recording. The rural excess was marked for cancer of the lip in both sexes, but less marked and clearly evident only in men for cancer of the eye. Three‐quarters of eye cancers are melanomas and the excess incidence in rural areas provides some weak support for the idea that exposure to sunlight contributes to the production of the disease.
Comparative analysis of the expression of the extracellular matrix protein tenascin in normal human fetal, adult and tumor tissues
Authors: Natali Pier Giorgio , Nicotra Maria Rita , Bigotti Aldo , Botti Claudio , Castellani Patrizia , Risso Anna Maria , Zardi Luciano
Published: February 2007

Tenascin (TN) is a high‐molecular‐mass oligomeric glycoprotein of the extracellular matrix (ECM) endowed with a programmed expression in embryonic life and a neo‐expression in the interstitium of some malignancies. Using monoclonal antibodies (MAbs) which identify human tenascin, we have conducted an extensive immunohistochemical analysis of TN expression in normal fetal and adult human tissues as well as in a wide variety of human tumors. Results of this study demonstrate that TN (1) is detectable in embryonic and fetal tissues at least from the 10th week of gestation; (2) is present in the interstitium of a variety of adult tissues of different embryonic origin; (3) may be neo‐expressed in the stroma of benign and malignant tumors; (4) has the ability to accumulate in a highly variable manner in the ECM of tumors of the same and of different histotypes.
Estradiol modulation of plasminogen activator production in organ cultures of human breast carcinomas: Correlation with clinical outcome of anti‐estrogen therapy
Authors: Mira‐Y‐Lopez Rafael , Osborne Michael P. , Depalo Angelo J. , Ossowski Liliana
Published: February 2007

We have studied the estradiol sensitivity of primary human breast carcinomas in organ culture in a prospective pilot series of 109 tumors. The effect on plasminogen activator (PA) production was used as the end‐point of estrogen action. We found that: (i) All tumors secreted detectable levels of urokinase‐type PA (uPA); the level of basal uPA production was markedly heterogeneous but showed a weak association with the level of estrogen receptor positivity (p = 0.049). (ii) Only 23.5% of the tumors secreted tissue‐type PA (tPA) in addition to uPA; a higher proportion of these tumors had histological characteristics indicative of good prognosis (18% vs. 3% of tumors secreting only uPA). (iii) Estradiol modulated uPA production and this effect was receptor‐mediated, (iv) Responsiveness to estradiol was limited to a subset (25 of 60 or 41.7%) of estrogen and progesterone‐receptor‐positive tumors, (v) Of 20 evaluable patients with lymph‐node and receptor‐positive breast cancer who received adjuvant anti‐estrogen therapy, 11 were identified as estradiol‐sensitive by the in vitro PA assay; of these, 10 had no evidence of disease after a median follow‐up period of 3+ years. In contrast, of 9 patients with tumors identified as estradiol‐insensitive, 4 developed metastases within 3+ years of follow‐up. (vi) Consistent with the previously reported inhibitory effect of corticosteroids on uPA production in organ cultures of human tumors, the basal culture level of uPA produced by tumors from patients receiving corticosteroids at the time of surgery was significantly lower than the level of uPA in the remaining tumors (p = 0.029). Also, tumors from patients receiving thyroid hormone, known to stimulate uPA in vitro, showed a slight trend toward increased production of uPA. These results show that hormone effects on tumor PA production are qualitatively similar in organ culture and in the host. This and the emerging individual correlation between sensitivity to estradiol in vitro, as determined by PA, and the clinical effectiveness of anti‐estrogen therapy, underscore the potential usefulness of the organ culture approach.
c‐erbB‐2 and ras expression levels in breast cancer are correlated and show a co‐operative association with unfavorable clinical outcome
Authors: Dati Claudio , Muraca Roberto , Tazartes Ornella , Antoniotti Susanna , Perroteau Isabelle , Giai Maurizia , Cortese Paolo , Sismondi Piero , Saglio Giuseppe , De Bortoli Michele
Published: February 2007

c‐erbB‐2 and ras expression was measured on tumor extracts from 132 human primary breast carcinomas, by immunoblotting analysis. Expression of the c‐erbB‐2‐encoded p 185 protein was observed in 39% of the samples and found to correlate with c‐erbB‐2 gene amplification, detected by Southern analysis in 19 of the 77 available tumor DNAs. P185 expression was linked to the absence of progesterone receptors, but it was not related to lymph‐node status or to other clinico‐pathological parameters. Levels of the ras‐encoded p2l proteins higher than in normal breast tissues were found in 71% of the samples. No significant correlation was seen between p21 level and the available clinical parameters. Conversely, there was a strong positive correlation between p2l and p185 levels. Analysis of follow‐up data revealed that p185 expression was associated with a shorter time to relapse and death. Most notably, the contemporaneous expression of p 185 and of high p21 levels was more effective than p185 expression alone in identifying cases with poor prognosis. The prognostic value of p185/p21 co‐expression was particularly significant in progesterone‐receptor‐positive tumors. Our data suggest that c‐erbB‐2 and ras may act synergistically to endow breast‐tumor cells with a highly aggressive phenotype.
Distribution of basement membrane antigens in human esophageal lesions: An immunohistochemical study
Authors: Mori Masaki , Shimono Reishi , Kido Akinori , Kuwano Hiroyuki , Akazawa Kouhei , Sugimachi Keizo
Published: February 2007

The distribution of basement membrane components, type‐IV collagen and laminin, was studied immunohistochemically in human samples of normal, hyperplastic, dysplastic and carcinomatous esophageal tissue. The expression of basement membrane components in normal, hyperplastic, and mildly and moderately dysplastic mucosa was characterized by a thick, continuous and linear staining pattern. In severe dysplasia and carcinoma in situ, the basement membrane was thinner and occasionally discontinuous. The distribution of basement membrane in invasive carcinomas varied greatly; well‐differentiated, cohesive tumors had a basement membrane, however, poorly‐differentiated tumors showing irregular cords, or individual cell infiltration, lacked this membrane at the tumor‐stromal interface. Many moderately‐differentiated tumors showed probable immature assembly of basement membrane components. The expression of basement membrane was also influenced by the extent of stromal inflammation. The absence or presence (staining pattern) of basement membrane components in esophageal squamous‐cell carcinoma did not correlate with the survival rate, but did correlate with the histologic differentiation of epithelial organization.
Expression of α‐sooth‐muscle actin in stromal cells of the uterine cervix during epithlial neoplastic changes
Authors: Cintorino Marcella , De Marco Esther Bellizzi , Leoncini Paolo , Tripodi Sergio A. , Ramaekers Frans C. , Sappino André P. , Schmitt‐Gräff Annette , Gabbiani Giulio
Published: February 2007

A total of 55 formalin‐fixed and paraffin‐embedded specimens of normal, inflamed and neoplastic uterine cervix have been studied in order to correlate the epithelial changes with the expression of α‐smooth‐muscle actin in stromal cells. This actin isoform is typical of smooth‐muscle cells, but appears also temporarily in fibroblasts during wound healing and permanently during fibrocontractive diseases and stromal reaction to epithelial tumors. While positive stromal cells were absent in normal and inflamed cervix, they accumulated in relation to neoplastic tissues. The number of α‐smooth‐muscle actin positive cells and the intensity of stain were related to the increasing grading of cervical intra‐epithelial neoplasia. Our results suggest that α‐smooth‐muscle actin is a marker of stromal‐cell reaction to the development of neoplastic lesions. The evaluation of α‐smooth‐muscle actin in stromal cells of the uterine cervix may be a useful adjunct to diagnostic criteria of cervical intra‐epithelial neoplasia and may help understanding of the mechanisms of mesenchymal‐epithelial interactions during neoplasia.
Prognostic significance of monoclonal antibody 3H‐1 reactivity with squamous‐cell head‐and‐neck cancers
Authors: Kearsley John H. , Leonard J. Helen , Takahashi Hiroyuki , Battistutta Diana , Parsons Peter G. , Moss Denis J.
Published: February 2007

We report the reactivity of a novel murine IgM monoclonal antibody (MAb), 3H‐1, in formalin‐fixed tissue from a series of 44 patients with squamous‐cell cancers (SCCs) of the upper aerodigestive tract. The antigen detected by 3H‐1 MAb is not expressed in simple squamous epithelia and only rarely in non‐squamous malignancies. The following staining patterns were found to be associated with a progressively unfavourable prognosis: membranous, diffuse cytoplasmic and focal cytoplasmic/nil staining. There were no statistically‐significant associations between focal cytoplasmic/nil staining and traditionally used prognostic parameters such as tumour size, nodal involvement or pathologic grade. However, multivariate analyses demonstrated that focal or nil staining was a significant independent prognostic factor for survival (p< 0.001) and was the only significant prognostic factor for relapse (p< 0.001). The converse applied to tumours with predominantly membranous staining (p= 0.004). 3H‐I MAb, with the advantage of relying on the pattern rather than the intensity of staining, makes it possible to identify different cellular phenotypic sub‐populations more accurately than by conventional means, and may ultimately improve our understanding of the mechanisms underlying transformation from a benign or proliferative state to a malignant one.
Case‐control study on stomach cancer in Germany
Authors: Boeing H. , Frentzel‐Beyme R. , Berger M. , Berndt V. , Göres W. , Körner M. , Lohmeier R. , Menarcher A. , Männl H. F. K. , Meinhardt M. , Müller R. , Ostermeier H. , Paul F. , Schwemmle K. , Wagner K. H. , Wahrendorf J.
Published: February 2007

A multicentric hospital‐based case‐control study was simultaneously performed in a high‐risk and a low‐risk area for stomach cancer in Germany, 143 patients with incident stomach cancer and 579 controls completing a retrospective interview about life style aspects. Periods of non‐centralized water supply or well water as the only source compared to life‐long central water supply, and preservation of meat by smoking it with spruce compared to no home smoking of meat, were significantly associated with an increased stomach cancer risk. Use of a refrigerator at home for 30 and more years compared to 24 years or less showed an inverse relationship, whereas salt intake estimated by questionnaire showed no relationship to stomach cancer risk. Tobacco smoking was negatively associated with risk for current smokers of cigarettes compared to non‐smokers but was presumably not causally related. After adjustment for other food constituents, only increased vitamin C consumption showed an inverse relation to risk. For food groups, increased consumption of fruit, citrus fruit, cheese and whole‐meal bread were associated with decreased risk. A similar effect was also seen for increased consumption of raw vegetables. Total vegetable consumption was not particularly associated with risk. Increased consumption of processed meat and of beer showed a positive association with risk whereas increased wine and liquor consumption showed a significant negative association. The association of alcoholic beverages with stomach cancer risk may reflect a particular life style rather than being causally related to risk.