bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishment and characterization of two epithelial tumor cell lines (hne‐1 and hone‐1) latently infected with epstein‐barr virus and derived from nasopharyngeal carcinomas
Authors: Yao Kaitai , Zhang Hai‐Ying , Zhu He‐Cheng , Wang Fu‐Xi , Li Gui‐Yuan , Wen Dong‐Seng , Li Ying‐Ping , Tsai Ching‐Hwa Ann , Glaser Ronald
Published: February 2007

Two epithelial tumor cell lines were established from biopsy specimens of 2 nasopharyngeal carcinomas (NPC) and designated HNE‐1 and HONE‐1. Uncloned HNE‐1 cells were found to be Epstein‐Barr virus (EBV) DNA‐positive when examined by Southern blot analysis up to passage 35, after which the EBV genome could no longer be detected. A similar loss of EBV DNA took place in uncloned HONE‐1 cells. However, HONE‐1 clone 40 cells are still EBV DNA‐positive up to passage 42 thus far and cell cultures contain 85–90% EBV nuclear antigen (EBNA)‐positive cells. The HNE‐1 cell line has been passaged more than 100 times and the uncloned HONE‐1 cells more than 90 times. The tumorigenicity of the HNE‐1 and HONE‐1 cells was demonstrated by tumor induction in nude mice. Karyotypic analysis of the HNE‐1 cells demonstrated an aneuploidy with a modal chromosomal number of 74 at passages 5 and 101 at passage 20; 18 marker chromosomes were identified. We have continued to map the EBV genome latently associated with the HNE‐1 and HONE‐1 cells using the Bam HI, EcoRI or Hind III restriction enzymes. Using EcoRI fragments A‐K as probes, we found that HNE‐1 EBV DNA is different from B95‐8 and HR‐1 EBV DNA in the EcoRI‐C region. The Bam HI map for HONE‐1 EBV DNA is very similar to the B95‐8 map; it contains the Bam HI‐Y fragment but without Bam HI B' and WI'. Differences were observed between HONE‐1 EBV DNA and B95‐8 DNA using the Hind III restriction enzyme. There was no evidence of spontaneous expression of the latent EBV genome in HNE‐1 cells, and attempts to induce replication of the latent EBV genome and rescue infectious virus have failed, suggesting a tightly restricted virus genome.
Murine monoclonal antibody recognizing a 90‐kDa cell‐surface determinant selectively lost by multi‐drug‐resistant variants of cem cells
Authors: Cianfriglia M. , Cenciarelli C. , Tombesi M. , Barca S. , Mariani M. , Morrone S. , Santoni A. , Samoggia P. , Alessio M. , Malavasi F.
Published: February 2007

We describe a murine IgG, monoclonal antibody (MAb56), specific for a cell‐surface protein structure (MC56 determinant) expressed by the human CEM cell line. A large band of approximately 90 kDa was identified as the main specific component of the MC56 determinant. Such a 90‐kDa protein is significantly associated with the drug‐sensitive phenotype, its expression being progressively reduced quantitatively in multi‐drug‐resistant (MDR) variants of CEM cells, according to the extent of drug resistance. In addition, the MC56 determinant is expressed de novo in drug‐sensitive revertant cell lines derived from MDR cells and unreactive with the MAb56. The MAb56 shows a high affinity towards the immunizing drug‐sensitive CEM cell line (Ka =1.86 × 109 L/mole) while not binding to MDR cell variants. The expression of the MC56 molecule on a variety of human cells and tissues makes such a cellular determinant a candidate as a marker for studying the MDR phenomenon both in vivo and in vitro.
B700, a melanoma‐specific antigen, catalyzes metabolism of prostaglandin E2
Authors: Farzaneh Nushin K. , Walden Thomas L. , Hearing Vincent J. , Gersten Douglas M.
Published: February 2007

B700 is an albumin‐like mouse‐melanoma‐specific antigen of unknown primary structure and biochemical function. The ability of mouse serum albumin to catalyze weak degradation of prostaglandin E2 has been utilized to compare functional similarities between B700 and mouse serum albumin. Both proteins catalyze the degradation of prostaglandin E2 to prostaglandin A2 and prostaglandin B2. This catalytic ability is related to the amino acid composition of the two proteins within the functional region rather than the 3‐dimensional configuration, since the activity is not altered upon boiling. The primary prostaglandin E2 metabolite in the presence of mouse serum albumin is prostaglandin B2, while prostaglandin A2 predominates in B700 catalyzed degradations. An additional product, presently unidentified, is produced during B700 catalyzed degradation of prostaglandin E2. Our studies indicate that the B700 protein has weak enzymatic activity for prostaglandin E2 similar to that of albumin. To our knowledge, B700 is the only melanoma antigen for which enzymatic activity has been demonstrated.
Til from renal‐cell carcinoma: Restimulation with tumor influences proliferation and cytolytic activity
Authors: Alexander Jeannine , Rayman Patricia , Edinger Mark , Connelly Robert , Tubbs Raymond , Bukowski Ronald , Pontes Edson , Finke James
Published: February 2007

TIL were cultured from human renal‐cell carcinoma (RCC) in 1,000 U/ml rIL2 and restimulated with autologous tumor in efforts to establish which conditions would best expand the number of lymphocytes cytotoxic for autologous tumor. Greater cell yields resulted from multiple restimulations of TIL with autologous tumor. In most instances, these TIL lysed autologous tumor better than TIL grown in rIL2 alone. Enhanced proliferation was seen also after restimulation of TIL with allogeneic RCC as well as with tumor cells of non‐renal origin. Although in some instances lysis of autologous tumor appeared to be specific, restimulation with autologous tumor did not consistently result in the generation of specific cytolytic T cells. Attempts to culture more specific cytolytic T cells by using 50 U/ml rIL2 were successful in expanding TIL with enhanced lytic activity; however, this activity was not specific for autologous tumor. The phenotype of the tumorrestimulated TIL generally did not change. In most of the TIL cultures, CD3+ CD4+ cells were predominant with low numbers of CD3+ Leu19+ cells and minimal numbers of CD3‐Leu 19+ cells. Thus, the cytotoxic response to tumor was mediated by T cells and not NK cells. Overall, our data indicate that restimulation of TIL with autologous tumor may be beneficial for growing larger numbers of cells which have increased lytic activity and for prolonging the presence of lytic activity among the expanded TIL.
Cancer procoagulant in serum of rats during development of experimental epithelioma
Authors: Mielicki W. , Wierzbicki R.
Published: February 2007

The activity of cancer procoagulant (CP) during the development of Guérin epithelioma was studied in the blood of Wistar rats. Blood was collected from the carotid artery and, after clotting, proteins adsorbing on aluminum hydroxide were removed from the serum. Then procoagulant activity was determined in the test system without factor VII by means of substrate S‐2222 specific for factor Xa. A statistically significant increase in the activity of CP in serum was detected, coinciding with the period of intensive tumor growth (15th–25th day of disease).
Persistent infection of rabbits with HTLV‐I: Patterns of anti‐viral antibody reactivity and detection of virus by gene amplification
Authors: Cockerell Gary L. , Lairmore Michael , De Barun , Rovnak Joel , Hartley Trudie M. , Miyoshi Isao
Published: February 2007

Two groups of rabbits were inoculated on the day of birth or at 4 weeks of age with a human T‐cell leukemia virus type‐I (HTLV‐I)‐infected and transformed rabbit cell line (Ra‐I). Rabbits seroconverted to HTLV‐I, as determined by indirect immunofluorescence, by 3 weeks after inoculation and remained persistently seropositive during a 22‐month period of observation. Seroconversion did not occur in salineinoculated controls. Using Western immunoblotting and radio‐immunoprecipitation, persistent seroconversion occurred against viral antigens p24, p55 and gp68, while reactivity to p19 was variable between rabbits. Using the polymerase chain reaction (PCR) with HTLV‐I gag and pol primer pairs, HTLV‐I sequences were demonstrable in peripheral blood mononuclear cells and other tissues collected at 70 and 90 weeks after inoculation. DNA extracts from normal rabbit tissue remained negative under the same conditions. No qualitative or quantitative changes in leukocytes or erythrocytes were detected in the infected rabbits and no clinical signs could be directly attributed to infection with HTLV‐I.
Multidirectional differentiation in a newly established human epithelioid sarcoma cell line (GRU‐1) with co‐expression of vimentin, cytokeratins and neurofilament proteins
Authors: Gerharz C. D. , Moll R. , Ramp U. , Mellin W. , Gabbert H. E.
Published: February 2007

A new permanent cell line (GRU‐1) derived from the lymph‐node metastasis of a human epithelioid sarcoma was established in tissue culture. Immunohistochemically, the original tumor had exhibited an intriguing potential for multidirectional differentiation with features of mesenchymal, epithelial and neural differentiation, evidenced by the co‐expression of vimentin, cytokeratins and neurofilament proteins, respectively. This capability for multidirectional differentiation was fully preserved in the cultured cells. GRU‐1 tumor cells proved to be uniformly positive for vimentin and a considerable proportion of the tumor cells exhibited a positive reaction for cytokeratins and neurofilament proteins. The neural markers neuron‐specific enolase (NSE) and synaptophysin were observed in a small proportion of GRU‐1 cells. Ultrastructurally, GRU‐1 cells showed desmoplastic activity in vitro, being enmeshed by collagen fibrils. DNA distribution, as studied by flow cytophotometry, revealed DNA‐diploidy (DNA index =1) and a G0/G1‐proportion of 70.5%. After heterotransplantation in nude mice, GRU‐1 tumor cells expressed vimentin and cytokeratin only, whereas the neural markers could not be further demonstrated.
Yolk‐sac carcinoma develops spontaneously as a late occurrence in slow‐growing teratoid tumors produced from transplanted 7‐day mouse embryos
Authors: Van Berlo R. J. , Oosterhuis J. W. , Schrijnemakers E. , Schoots C. J. F. , De Jong B. , Damjanov I.
Published: February 2007

Seven‐day embryos of BALB/c mice transplanted underneath the kidney capsule of adult syngeneic recipients form either benign teratomas or teratocarcinomas, which can be distinguished from one another histologically at 8 weeks postembryonic transplantation. Embryo‐derived (ED) teratomas were allowed to remain in the host for an additional period up to 1 year after embryo transplantation, to test their malignant potential. It was found that a considerable number of slow‐growing small tumors derived from embryonic transplant give rise to parietal yolk‐sac carcinomas. A proportion of these tumors contained foci of visceral yolk‐sac and trophoblastic differentiation, which gradually disappeared in successive transplantations. We conclude that parietal yolk‐sac carcinoma develops as a late event in some ED teratomas. These malignant tumors originate either from small foci of yolk sac originally included in the grafted embryo or, more likely, from the yolk sac formed from the differentiating embryonic stem cells.
Increase in topoisomerase‐II‐mediated dna breaks and cytotoxicity of VP16 in human U937 lymphoma cells pretreated with low doses of methotrexate
Authors: Lorico Aurelio , Boiocchi Mauro , Rappa Germana , Sen Soumitra , Erba Eugenio , D'Incalci Maurizio
Published: February 2007

Pre‐treatment with low, non‐toxic concentrations (0.04μM) of methotrexate (MTX) for 16 hr increased etoposide (VP16)‐induced growth inhibition and cytotoxicity in the U937 human histiocytic lymphoma cell line. VP16 cytotoxicity was significantly potentiated when the drug was given for 2 hr immediately after MTX pre‐treatment or between 2 and 4 hr or 4 and 6 hr after recovery from MTX pre‐treatment. By 24 hr after recovery from MTX, no potentiation was evident. The increased cytotoxicity of VP16 was associated with an increase in drug‐induced DNA breaks as assessed by the alka‐line elution method after proteinase K digestion. The amount of DNA single‐strand breaks (DNA SSB) increased when the drug was given 0, 2, and 4 hr after MTX pre‐treatment. DNA SSBs induced by the drug between 6 and 24 hr after MTX pre‐treatment were similar to those seen in cells without pre‐treatment. The amount of DNA double‐strand breaks (DNA DSB) caused by VP16 increased significantly when the drug was given 4 hr after recovery from MTX pre‐treatment. VP16‐induced DNA DSBs were still higher 6 hr after MTX pre‐treatment, but by 24 hr they were similar to those observed in MTX‐untreated cells. Flow cytometric analysis showed that MTX pre‐treatment was causing an accumulation of U937 cells at the G1‐S boundary of the cell cycle. When MTX was removed, a wave of synchronization followed. Using Western blot electrophoresis and polyclonal antibodies to antitopoisomerase II, we found that MTX pre‐treatment raised the cellular topoisomerase II content. Our findings suggest that the potentiation of VP16 cytotoxicity on U937 cells by low, non‐toxic MTX pre‐treatment is due to a larger fraction of S‐phase cells containing a higher concentration of topoisomerase II, which is the putative target of VP16 action.
Effect of vip on the glycogen metabolism of human colon adenocarcinoma cells studied by 13C nuclear magnetic resonance spectroscopy
Authors: Galons Jean‐Philippe , Fantini Jacques , Vion‐Dury Jean , Cozzone Patrick J. , Canioni Paul
Published: February 2007

Metabolic pathways of glucose utilization have been investigated in a human colon adenocarcinoma cell line (HT29) using carbon‐13 Nuclear Magnetic Resonance spectroscopy. HT29 cells were adapted to grow on a polystyrene beaded microcarrier and were perfused when attached to the beads in a specially designed NMR cell. Abnormalities in carbohydrate metabolism already observed in several cancer cells were studied in HT29 cells fed with (I‐13C)‐enriched glucose. The cells were first perfused with a glucose‐free medium for 2 hr in order to deplete the intracellular store of glycogen, and they were subsequently perfused with a medium containing enriched glucose at an initial concentration of 5.5 mM. Sequential 13C‐NMR spectra, recorded at 100.5 MHz (5 min accumulation), show that HT29 cells were able to utilize glucose through the glycolytic pathway while storing glucose as glycogen (glucose was utilized at a rate of 3.9 μmol/mg protein/hr). The glycolytic activity determined by the amount of lactic acid produced was 4.6 μM/mg protein/hr, corresponding to the formation of 1.2 lactic acid per glucose molecule. Glycogen accumulation corresponded to 16 μg/mg of protein. Treatment of HT29 with 10 nM vasoactive intestinal peptide (VIP) induced a transient decrease in the level of labelled glycogen to 50% of the initial value. Control level was recovered 12 min after VIP loading.
Inhibition of growth and squamous‐cell differentiation markers in cultured human head and neck squamous carcinoma cells by β‐all‐trans retinoic acid
Authors: Jetten Anton M. , Kim Jun S. , Sacks Peter G. , Rearick James I. , Lotan Dafna , Hong Waun K. , Lotan Reuben
Published: February 2007

Vitamin A and some of its metabolites such as β‐all‐trans retinoic acid (RA) have been implicated in the regulation of differentiation of normal and malignant epithelial cells in vivo and in vitro. In the present study effects of RA on the growth and differentiation of 7 cell lines derived from human head and neck squamous‐cell carcinomas (HNSCCs) were examined. RA (>0.01 μm) inhibited the proliferation in monolayer culture of 6 of 7 HNSCC cell lines. One cell line (UMSCC‐35) was very sensitive, 5 (UMSCC‐10A, ‐19, ‐30, ‐22B and HNSCC 1483) were moderately sensitive, and I (HNSCC 183) was insensitive. Three of the cell lines (UMSCC‐22B, ‐30, and HNSCC 1483) were capable of forming colonies in semisolid medium—a capability that was suppressed by RA. The HNSCC cell lines expressed various levels of the squamouscell differentiation markers type 1 (particulate, epidermal) transglutaminase (TGase) and cholesterol sulfate (CS). RA treatment (1 μ, 6 days) decreased TGase activity by more than 50% in 3 (UMSCC‐10A, ‐228 and 1483) of the 7 cell lines, and the effect on UMSCC‐22B was dose‐dependent. Type II TGase (soluble, tissue type) activity was detected in 3 cell lines, and after RA treatment its activity increased in HNSCC 1483 and 183 cells and decreased in UMSCC‐19. Following RA treatment, CS levels decreased by 20, 25, 70, 76, 89 and 91% in cell lines UMSCC‐30, ‐10A, 183, UMSCC‐35, ‐22B, and HNSCC 1483, respectively. The suppression by RA of CS accumulation in the 1483 cells was dose‐dependent. Cholesterol sulfotransferase activity, which is responsible for CS synthesis, was suppressed by 40–97% after RA treatment of UMSCC‐19, ‐22B, and HNSCC 1483. Our results demonstrate that RA inhibits the growth and decreases the level of 2 squamous differentiation markers in HNSCC cells.
Tumour cells which develop resistance to cytolysis by tumour necrosis factor have a different glycoform of a 105‐kda glycoprotein and lose the capacity to invade and metastasize
Authors: Lynne Neale M. , Fiera Rosemary A. , Matthews Nicholas
Published: February 2007

A plastic‐adherent variant of human myelomonocytic leukaemia cells (U937) is highly susceptible to direct TNF cytolysis in vitro. Previously, we found that a subline selected for resistance to TNF cytolysis (U937/R) was much less motile and more plastic‐adherent than the parental line. In the present study we show that U937 and U937/R cells have different glycoforms of a 105‐kDa cell‐surface glycoprotein. This protein is predominantly N‐glycosylated and has the physicochemical properties of the LAMP‐1 glycoprotein. In nude mice, U937 cells are highly malignant whereas U937/R cells form a benign, encapsulated tumour. Therefore, possession of a different glycoform of the 105‐kDa glycoprotein by U937/R cells correlates not only with loss of TNF susceptibility but also with reduced invasiveness and metastasis.
DNA‐ploidy as prognostic factor in prostatic carcinoma
Authors: Haugen O. A. , Mjølnerød O.
Published: February 2007

DNA‐ploidy in 143 cases of prostatic carcinoma was assessed by flow cytometric analysis of paraffin‐embedded biopsy material. The majority of the tumours (64.3%) were diploid, but in advanced stages the DNA‐aneuploidy rate increased from 15 to over 60%. No hypoploid tumour was observed and most of the hyperploid tumours were neartetraploid. DNA‐aneuploidy was also strongly related to histological grade. Survival analysis using Cox multivariate regression model revealed that low histological grade (high Gleason score), advanced stage and increased level of prostatic acid phosphatase were the most important prognostic factors. DNA‐ploidy per se did not contribute independently as a predictor of survival.
A case‐control study of hepatocellular carcinoma in osaka, Japan
Authors: Tsukuma Hideaki , Hiyama Tomohiko , Oshima Akira , Sobue Tomotaka , Fujimoto Isaburo , Kasugai Hiroshi , Kojima Junnosuke , Sasaki Yo , Imaoka Shingi , Horiuchi Naruto , Okuda Shigeru
Published: February 2007

A case‐control study was undertaken to evaluate the roles of hepatitis B virus (HBV), blood transfusion, alcohol drinking and cigarette smoking in the etiology of hepatocellular carcinoma (HCC) in Osaka, Japan. A total of 229 cases and 266 hospital controls were included in our study. The relative risks of HCC obtained after adjustment for age, sex and other important variables were 14.3 (95% confidence interval (CI): 5.7–36.3) for HBsAg positives, 4.3 (95% CI: 1.9–9.6) for blood recipients and 3.2 (95% CI: 2.0–5.1) for heavy drinkers. A statistically significant dose‐response relationship was observed between the risk of HCC and total alcohol consumption. The overall risk for HCC was also significantly elevated among smokers; however, there was no consistent dose‐response relationship between the risk and cigarette consumption. We conclude that HBV, blood transfusion and excessive alcohol drinking play important roles in the etiology of HCC in Osaka, Japan. Further investigation is needed to clarify the possible etiological role of smoking.
The 4th nation‐wide study of adult T‐cell leukemia/lymphoma (ATL) in Japan: Estimates of risk of ATL and its geographical and clinical features
Authors: Tajima K. ,   The T‐ and B‐Cell Malignancy Study Group,   Co‐Authors
Published: February 2007

To estimate the annual incidence of adult T‐cell leukemia/lymphoma (ATL) by district in Japan, a large‐scale nationwide survey of ATL and of non‐Hodgkin's lymphoma was performed in 1988. Questionnaires for the registration of ATL and of T‐cell and non‐T‐cell lymphoma were distributed to the physicians in charge of this survey in 1,287 hospitals with 200 or more beds throughout Japan. From the positive rate of anti‐HTLV‐I antibody in adults, the annual incidence of ATL was estimated at 697, independently of the present survey. In fact, 657 cases (47% of the estimated number), newly diagnosed during the 2 years January 1986 to December 1987, were registered from 191 general hospitals throughout Japan. Major results obtained from the present survey are as follows: (1) among all ATL cases registered, 51% were from Kyushu and 29% were from metropolitan areas (Kanto, Chubu and Kinki) and most, but not all, patients with ATL in the metropolitan areas had come from the ATL‐endemic areas and settled in the metropolitan areas; (2) the estimated annual incidence rates of ATL per million adults were 40.4 in males and 26.4 in females in Kyushu, the overall risk of ATL being 1.5 times as high in males as in females; (3) the age‐specific incidence rate in Kyushu increased steeply with age until the age of 70, and then decreased markedly in both sexes; (4) the ratio of T‐cell versus non‐T‐cell lymphomas was 2.9 in Kyushu but 0.5 in other districts of Japan, however, this difference regressed to the average for the whole of Japan if ATL cases were excluded; (5) 26.5% of patients with ATL had a family history of cancer, and among these, 14 (8.2%) were ATL, 21 (12.2%) were lymphoma and 17 (9.9%) were hematopoietic malignancies, the incidence of which was markedly higher than in the general population; (6) with regard to clinicopathological features of ATL, there were more advanced cases in south Kyushu than in other districts, however, these differences were not statistically significant. To clarify the chronological changes and geographical variations in the annual incidence of ATL in Japan, continuous systematic nationwide surveillance is necessary and further nation‐wide studies are being prepared.
A simplified immuno‐enzymetric assay of the epidermal growth factor receptor in breast tumors: Evaluation in 282 cases
Authors: Grimaux M. , Mady E. , Remvikos Y. , Laine‐Bidron C. , Magdelenat H.
Published: February 2007

The epidermal growth factor receptor (EGF‐R) is currently being investigated in human clinical oncology, and particularly in breast cancer, as a potential prognostic factor and a biological target for therapy. As an alternative to the 125I‐EGF binding assay, we propose a sensitive immuno‐enzymetric assay (IEMA) suitable for EGF‐R assay in breast cancer. The assay is performed on solubilized extracts of the 105,000 g pellet of a tumor homogenate, allowing estrogen (ER) and progesterone (PR) assays to be made on the cytosol. The IEMA is performed on 96‐well plates coated with the monoclonal anti‐EGF‐R antibody RI, through an anti‐mouse IgG2b bridge. Trapped EGF‐R in the samples is covered by a second monoclonal antibody (MAb), 528, and revealed by an antilgG2a‐peroxidase complex. The sensitivity is I fmol/mg membrane protein, and the assay can be performed on tissue samples down to 50 mg. Two hundred and twenty primary ductal breast carcinomas assayed by this method showed a log normal distribution with a modal value of 8 fmol/mg prot., a mean at 18 and a median at 13 fmol/mg prot. EGF‐R‐rich tumors (>20 fmol/mg prot.) were highly correlated with the absence of estrogen receptors and/or with a high histological grade (SBR III). Our data demonstrate the validity of the IEMA assay of EGF‐R in human breast tumors.
Somatostatin receptors are present in small‐cell but not in non‐small‐cell primary lung carcinomas: Relationship to EGF‐receptors
Authors: Reubi J. C. , Waser B. , Sheppard M. , Macaulay V.
Published: February 2007

Sixteen primary human lung tumours were analysed for their content of somatostatin receptors using receptor autoradiography with somatostatin‐28 and somatostatin octapeptide analogues as radio‐ligands. Two out of 4 small‐cell lung carcinomas were somatostatin receptor‐positive, with a high density of homogeneously distributed receptors on tumour tissue only. Somatostatin receptors were characterized in one of the tumours in homogenate binding assay as saturable, high‐affinity binding sites (KD =0.53 nM) with a number of sites (Bmax) equivalent to 189 fmoles/mg protein. These sites were specific for somatostatin, since only biologically active somatostatin analogues but not unrelated peptides showed high‐affinity binding. Both receptor‐positive patients had limited disease; furthermore, the small‐cell lung carcinoma patient with the longest survival was receptor‐positive, while the one with the shortest survival was receptor‐negative. None of the 12 non‐small‐cell lung carcinomas (5 squamous carcinomas, 7 adenocarcinomas) contained somatostatin receptors. For comparison, epidermal growth factor receptors were found in all non‐small‐cell lung carcinomas. Neuroendocrine features (synaptophysin, chromogranin, neuronspecific enolase, protein gene product 9.5) were present in all small‐cell lung carcinomas but absent in non‐small‐cell lung carcinomas. Given the receptor‐mediated action of somatostatin in other neuroendocrine tumours, these data may have a bearing on the clinical application of somatostatin analogues in patients with small‐cell lung carcinomas.
Height and cancer risk in a network of case‐control studies from northern Italy
Authors: La Vecchia Carlo , Negri Eva , Parazzini Fabio , Boyle Peter , D'Avanzo Barbara , Levi Fabio , Gentile Antonella , Franceschi Silvia
Published: February 2007

The relationship between self‐reported height and cancer risk was investigated in an integrated series of case‐control studies including 273 cases of cancer of the oesophagus, 474 of the stomach, 558 of the colon, 352 of the rectum, 227 of the liver, 267 of the pancreas, 110 of the larynx, 2,388 of the breast, 545 of the cervix uteri, 563 of the endometrium, 688 of the ovary, 80 of the prostate, 263 of the bladder, 105 of the kidney, 43 Hodgkin's disease, 152 non‐Hodgkin's lymphomas, 109 multiple myelomas, and a total of 5,574 controls admitted to hospital for acute, non‐neoplastic conditions. No significant positive trend in risk was observed for any of the cancer sites considered, and some suggestion of elevated risks for the upper quintile of height was observed only for prostate (relative risk, RR =1.4), kidney (RR =2.7) and colon (RR =1.2) in males (but not in females). For breast cancer, all the RRs for subsequent quintiles of height were close to unity. Four neoplasms showed significant inverse trends with height: oesophagus (RR =0.7 for highest vs. lowest quintile), cervix (RR =0.4), endometrium (RR =0.7) and ovary (RR =0.6). For oesophagus and cervix the trends could be explained, at least in part, in terms of social class correlates (multivariate RR 0.8 and 0.5, respectively), while for endometrium they could possibly be related to an inverse correlation between height and body mass (multivariate RR 0.9). Thus, our study did not support the hypothesis that nutrition in childhood and adolescence (which in this population is a determinant of adult height) is directly related to the subsequent risk of cancer at several major cancer sites. A number of inverse associations emerged, which may be either spurious and incidental, or suggest that poorer nutrition early in life may be an unfavourable indicator of the subsequent risk of selected neoplasms.
Establishment of an EBV‐positive lymphoblastoid cell line that grows as a lymphoma in nude mice and expresses membrane CD2 molecules
Authors: Roncella S. , Ramarli Dunia , Cooper M. K. , Forni M. , Caretto Patrizia , Rowe M. , Celle Paola Francia Di , Sessarego M. , Foá R. , Forni G. , Burrows P. , Pistoia V. , Ferrarini M.
Published: February 2007

We describe a human lymphoblastoid cell line (LCL), called ZS, that originated spontaneously from the cultures of gamma‐irradiated (50 Gy) peripheral‐blood mononuclear cells of a normal donor. When injected subcutaneously in sublethally irradiated, splenectomized and anti‐asialo‐GM1‐treated nude mice, ZS cells invaded the lymph nodes, that appeared 10 to 50‐fold enlarged in all of the mice tested. Furthermore, ZS cells expressed a typical T‐cell surface structure, the CD2 molecule, detectable by a variety of different anti‐CD2 monoclonal antibodies (MAbs). However, other T‐cell markers were not found, with the possible exception of a truncated messenger of the β chain of the T‐cell receptor and ZS cells could be identified as B cells since they (i) expressed a battery of markers of the resting and activated B cells, (ii) displayed a monoclonal rearrangement of the lgH chain locus and (iii) synthesized lgM K molecules.

The Epstein‐Barr virus (EBV) genome was detected in ZS cells in approximately ten copies per cell by DNA hybridization techniques. Furthermore, the cells were positive for EBV nuclear antigens (EBNA). Western blotting analysis of EBV encoded antigens demonstrated clear differences with those present in the B 95.8 virus‐producer cell line, indicating that ZS cells were not infected by EBV in vitro and that they already harbored the virus in vivo. ZS cells formed colonies in vitro with a high cloning efficiency and displayed chromosomal abnormalities in all of the mitoses (karyotype 47, xy, +13,–14, 8p+, 21p+, +m). In spite of these malignant features, ZS cells expressed the full range of EBV latent proteins as usually do “normal” LCSs and did not have any of the chromosomal abnormalities that juxtapose the c‐myc oncogene to one of the genes coding for immunoglobulir molecules.
Effect of ornithine decarboxylase inhibitor on tetragastrin treatment of gastric carcinogenesis induced by N‐methyl‐N'‐nitro‐N‐nitrosoguanidine in wistar rats
Authors: Tatsuta Masaharu , Iishi Hiroyasu , Baba Miyako , Taniguchi Haruo
Published: February 2007

The effects of combined administration of tetragastrin and the ornithine decarboxylase inhibitor 1,3‐diaminopropane (DAP) on the incidence and number of gastric cancers induced by N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG), and the BUdR labelling indices of the fundic and antral mucosae, were investigated in inbred Wistar rats. Rats were given drinking water containing 2.5 g/l of DAP ad libitum and received alternate‐day injections of 1 mg/kg body weight of tetragastrin in depot form after 25 weeks of oral treatment with MNNG. At week 52, prolonged administration of tetragastrin alone resulted in a significant reduction in the incidence and number of gastric cancers and a significant increase or decrease in the labelling indices of the fundic and antral mucosae, respectively. Concomitant administration of tetragastrin and DAP had no effect on the inhibition by tetragastrin of gastric carcinogenesis. With this treatment, the labelling index was significantly reduced in the fundic mucosa but not in the antral mucosa. These results suggest that ODC inhibitor does not attenuate tetragastrin inhibition of gastric carcinogenesis, and that anti‐trophic action of tetragastrin on antral mucosa may be related to tetragastrin inhibition of gastric carcinogenesis.
Role of CD18 in lymphokine, activated killer (LAK) cell‐mediated lysis of human monocytes: Comparison with other lak targets
Authors: Kay Blanchard D. , Hall Robert E. , Djeu Julie Y.
Published: February 2007

The role of CD 18, identified as the beta chain of the CD 11 family of adhesion glycoproteins, in the lysis of normal autologous monocytes by interleukin‐2‐activated killer (LAK) cells was explored. The addition of several preparations of anti‐CD18 monoclonal antibodies (MAbs) to the incubation mixture of LAK cells and various target cells indicated that lysis of autologous monocytes, K562 erythroleukemia tumor cells, FMEX melanoma tumor cells, and fresh ovarian tumor cells were readily inhibited by all anti‐CD 18 antibodies tested. Kinetic experiments demonstrated that significant inhibition of lysis occurred if RH1‐38 antibody was added up to 2 hr after LAK cells were added to target cells. By the use of selective coating of targets and effector cells with RH1‐38, it was determined that anti‐CD 18 antibody inhibited lysis at the effector cell level but not at the target cell level, although CD18 was detectable on the surface of monocyte targets by FACS analysis and immunoprecipitation. Furthermore, specific binding of LAK cells to all targets tested was not affected by the presence of anti‐CD 18, indicating that lysis of target cells was blocked at a post‐binding event. Finally, of the 3 alpha chains associated with CD18, only antibodies to LFA‐1 (CD 11 a) partially blocked binding of LAK cells to monocytes and tumor cells. It is possible, then, that both CD 11a and CD18 may work in concert to effect the lysis of target cells by LAK cells.
Residual immunity of athymic NCr/sed nude mice and the xenotransplantation of human tumors
Authors: Silobricic Vlatko , Zietman Anthony L. , Ramsay Jonathan R. , Suit Herman D. , Sedlacek Robert S.
Published: February 2007

This study assessed the residual immunity possessed by NCr/Sed (nu/nu) athymic nude mice and examined strategies to reduce it in order to enhance the transplantability of human tumors for experimentation. Adult (8‐week‐old) female mice had fewer T cells (11%) and more B and NK (asialo‐GM1‐positive [ASGM1+]) cells in their spleen than euthymic (nu/+) controls. The number of phenotypically mature T cells increased with age, peaking at 16 weeks. ASGM1+ cells also increased in number over time, although the NK‐activity decreased after 12 weeks. B cells remained relatively constant in number. Athymic NCr/Sed nude mice displayed reactivity against a human squamous carcinoma xenograph (FaDu), in a Winn's test and TD50 assay. Immunity against xenografts (TD50 assay) was significantly lower (by a factor of 2) in 4‐week‐old than in 12‐week‐old nude mice. Similarly, a significant 2‐fold reduction in TD50 was obtained after a single intraperitoneal injection of cyclophosphamide into 8‐week‐old animals. Chronic (>8 weeks) exposure of the nude mice to subcutaneously administered β‐estradiol markedly reduced the number of splenic NK cells and their cytolytic activity, but the TD50 reduction was not statistically significant (p =0.1). Six Gray whole‐body irradiations (WBI) had been shown to produce a highly significant, 3‐fold reduction in the TD50 for FaDu. Flow cytometric analysis of splenic lymphoid cells from whole‐body‐irradiated recipients revealed: (a) marked initial depletion in the absolute numbers of lymphoid cells; (b) marked and long‐lasting depletion of T cells, with slow and minimal recovery only evident between 6 and 12 weeks; (c) rapid, almost complete, depletion of B cells with prompt and partial recovery after 2 weeks; (d) depletion of NK cells and NK activity, with recovery by 10 weeks. No change in the number or phagocytic capacity of resident peritoneal macrophages was seen. These data give further support to a postulated role for residual T cells in the xenoreactivity of NCr/Sed nude mice.
Cytokine‐mediated modulation of HLA‐class II, ICAM‐1, LFA‐3 and tumor‐associated antigen profile of melanoma cells. comparison with anti‐proliferative activity by RIL1‐β, RTNF‐α, RIFN‐γ, RIl4 and their combinations
Authors: Mortarini Roberta , Belli Filiberto , Parmiani Giorgio , Anichini Andrea
Published: February 2007

Nine different human melanomas and 16 clones, isolated from 2 of them, were characterized for susceptibility to rIL1‐β, rIL4‐, rTNF‐α‐ and rIFN‐γ‐mediated effects on proliferation and surface expression of class‐II HLA (DR and DP), ICAM‐1 and LFA‐3 molecules and of 3 tumor‐associated antigens (recognized by MAb 763.74T, 149.53 and R24). In spite of marked inter‐ and intra‐tumor heterogeneity for susceptibility to the effects of each cytokine, the most frequent upregulation was induced on the HLA class‐II antigens by rIFN‐γ and on adhesion molecules by rIFN‐γ, rTNF‐α and rlL1‐β, while tumor‐associated antigens were often down‐modulated by rIFN‐γ. Tumor heterogeneity was also evident on tumorcell proliferation with an apparent hierarchy in the frequency and extent of inhibitory effects: rIFN‐γ >rTNF‐α >rIL1‐β =rIL4. Combinations of 2 cytokines resulted in rare and limited changes in the antigenic profile in comparison to the effects seen with single factors, while the combination of rTNF‐α and rIFN‐γ resulted in significant synergistic antiproliferative effects on most tumor cells and clones. Taken together, these results indicate that single cytokines can profoundly affect the antigenic profile of melanoma cells, while strong tumor‐growth inhibition is often achieved by combinations of 2 cytokines acting in synergism.
Regulation of C‐FGR proto‐oncogene expression in epstein‐barr virus infected B‐cell lines
Authors: Patel Mukesh , Leevers Sally J. , Brickell Paul M.
Published: February 2007

We and others have previously shown that in vitro conversion of Epstein‐Barr virus (EBV)‐negative Burkitt lymphoma (BL) cell lines with the immortalizing B95‐8 strain of EBV results in a marked elevation in levels of c‐fgr proto‐oncogene mRNA. We now show, using a nuclear run‐off assay, that this induction results from an increase in the rate of transcription of the c‐fgr gene. We also show that BL cell lines freshly converted with the non‐immortalizing HR‐I strain of EBV do not accumulate higher levels of c‐fgr mRNA, suggesting that EBNA‐2 and/or LMP, the genes which are deleted in the HR‐I strain, may be involved in the pathway which leads to changes in c‐fgr gene expression. In order to assess the generality of a role for the c‐fgr gene in the response of B‐lymphocytes to EBV‐infection, which is controversial, we have analysed c‐fgr expression in 6 freshly immortalized cell lines established by EBV (B95‐8) infection of B‐lymphocytes from the peripheral blood of normal adults and of adults with rheumatoid arthritis, from cord blood, and from foetal liver. All 6 cell lines expressed c‐fgr mRNA at elevated levels compared to EBV‐negative BL cell lines.
Enhanced suppression of human myeloid leukemic cell lines by combinations of IL‐6, LIF, GM‐CSF and G‐CSF
Authors: Maekawa Taira , Metcalf Donald , Gearing David P.
Published: February 2007

The interactions of purified recombinant human leukemia inhibitory factor (LIF), interleukin‐6 (IL‐6), granulocyte colony stimulating factor (G‐CSF), and granulocyte‐macrophage CSF (GM‐CSF) on the clonogenicity of HL60 cells and U937 cells were studied in vitro. 11‐6 alone strongly suppressed colony formation by U937 cells with induction of differentiation and loss of clonogenicity. GM‐CSF interacted synergistically with IL‐6 to further reduce colony number and suppress the growth of clonogenic cells formed by HL60 and U937 cells. LIF synergized with IL‐6 to reduce colony number and enhance the suppression of the clonogenic U937 cells. The results suggest that these 4 glycoproteins, acting alone or in combination, may be able to suppress human leukemia cells of appropriate type and be of value in the clinical management of myeloid leukemia.
Age at first and second births and breast cancer risk in biparous women
Authors: Negri E. , La Vecchia C. , Duffy S. W. , Bruzzi P. , Parazzini F. , Day N. E.
Published: February 2007

The role of age at first and at second birth on subsequent breast cancer risk was analyzed using pooled data from 2 hospital‐based case‐control studies conducted in Italy, for a total of 1,200 biparous cases and 987 controls. Compared with women who gave birth for the first time below age 20, the relative risks were above unity for those with later first birth, even after allowance for age at second birth, although the trend was inconsistent across subsequent strata. A similar direct trend in risk was observed in relation to age at second birth: compared with less than 25 years and after allowance for age at first birth, the point estimates were 1.2, 1.4 and 1.4 for 25–29, 30–34 and ≥35 (p for linear trend = 0.04). The results for age at first and at second birth were similar in the 2 studies pooled in this analysis. A significant interaction with age was observed in relation to age at first and at second birth. In younger women (below age 50) a strong and direct association with age at first birth was found, while no apparent protection was conveyed by earlier second birth. Among older women (aged 50 or over), there was no apparent relationship with age at first birth after allowance for age at second, but the role of age at second birth was independent and statistically significant. Thus, our study confirms an independent and significant role of age at second birth in biparous women, after allowance for age at first birth, and indicates that, after reciprocal allowance, the role of first and second birth was not apparently different. The relative risks for both variables were quantitatively moderate, and may be influenced by age or other temporal variables.
Cancer mortality among japanese residents of the city of säo paulo, Brazil
Authors: Tsugane Shoichiro , Gotlieb Sabina L. D. , Laurenti Ruy , de Souza Jose M. P. , Watanabe Shaw
Published: February 2007

Death certificates of Japanese residents of the city of Säo Paulo, Brazil from 1979 to 1981 were analyzed for cancer deaths by means of the standardized mortality ratio (SMR) and the standardized proportional mortality ratio (SPMR). Compared with residents of Japan, a significantly higher SMR value was obtained from Japan‐born residents of Säo Paulo for prostate cancer, whereas lower values were obtained for cancer of the liver and gall‐bladder in both sexes, of the esophagus and rectum in males, and of the lung in females. SMR values were higher for cancer of the stomach in both sexes but lower for those of the esophagus and prostate in males and of the gall‐bladder and breast in females, when compared with the general population of Säo Paulo. Among Japan‐ and Brazil‐born residents, stomach cancer in women revealed a significant stepwise decrease by generation when SPMR was used as an indicator. The high proportion of stomach cancer in males, however, was as high among the Brazil‐born generation as in Japan. The SPMR of liver cancer decreased to the low level of the general population of Säo Paulo, even among the first generation. These changes in cancer patterns are discussed in relation to those among Japanese residents in the United States.
Body mass index and risk of breast cancer. A prospective study of 23,826 norwegian women
Authors: Vatten Lars J. , Kvinnsland Stener
Published: February 2007

The association between body mass index (BMI) and the incidence rate of breast cancer has been examined in 236 cases of breast cancer that developed among 23,826 Norwegian women during 11 to 14 years of follow‐up. At the time of height and weight measurement they were 35 to 51 years of age, and at the end of follow‐up their age was between 46 and 63 years. There was an overall age‐adjusted incidence rate ratio (IRR) of 0.52 (95% confidence limits, 0.34 and 0.77) for women in the highest quartile of BMI compared to women in the lowest quartile, which was confined to an effect observed among women who were diagnosed at age 50 or earlier (IRR = 0.36). The association with BMI displayed an inverse dose‐related trend (X2 for trend = 14.22, p < 0.001). The negative trend was particularly pronounced among non‐smoking women (X2 = 14.63), and no clear trend associated with BMI was observed among women who smoked 10 or more cigarettes per day (X1 = 0.41), indicating an interaction between BMI and cigarette smoking (X2 interaction = 3.86, p = 0.05). We thus suggest that there is a negative association between body mass index and risk of breast cancer among premenopausal women.
Lymphocytic infiltration and cytotoxicity under hypoxic conditions in the EMT6 mouse mammary tumor
Authors: Loeffler David A. , Keng Peter C. , Baggs Raymond B. , Lord Edith M.
Published: February 2007

Infiltration of lymphocytes, neutrophils and macrophages was evaluated in hypoxic and well‐oxygenated areas of the EMT6 mouse mammary adenocarcinoma, by in vivo staining with the fluorescent dye Hoechst 33342 followed by cell sorting on the basis of fluorescence intensity. Tumors were grouped by days post‐injection (days 11–14, 15–17 and 20–27). As lymphocytes are the only host cell population in this tumor model to possess lytic activity against EMT6 tumor cells, the ability of sensitized T lymphocytes to lyse syngeneic EMT6 cells was examined under conditions of varying oxygen concentrations. Infiltrating lymphocytes were detected to the same extent in cell fractions from both areas in all tumors. In contrast, neutrophils were found in significantly higher percentages in the hypoxic population than in the well‐oxygenated cell fraction of all but the largest tumors. Macrophages were present in significantly higher percentages in the well‐oxygenated fraction than in the hypoxic fraction of day‐11 to ‐14 tumors. Extreme radiobiological hypoxia (0% O2) resulted in a significant decrease in T‐cell‐mediated lysis of EMT6 tumor cells, compared to lysis in room air (20% O2), but lysis was not impaired under conditions of mild radiobiological hypoxia (1% O2). Our study indicates that host‐cell infiltration into areas of differing oxygenation may be quantitated via in situ Hoechst staining followed by cell sorting; in the EMT6 tumor, lymphocytes appear to infiltrate hypoxic areas to the same extent as well‐oxygenated areas, and T‐lymphocyte killing of syngeneic tumor cells is significantly reduced, although still present, under these hypoxic conditions.
Inhibitory effects of 9‐(2‐Phosphonylmethoxyethyl)adenine and 3′‐azido‐2′,3′‐dideoxythymidine on tumor development in mice inoculated intracerebrally with moloney murine sarcoma virus
Authors: Balzarini Jan , Sobis Halina , Naesens Lieve , Vandeputte Michel , De Clercq Erik
Published: February 2007

9‐(2‐Phosphonylmethoxyethyl)adenine (PMEA), a potent inhibitor of human immunodeficiency virus (HIV), caused a dose‐dependent suppression of tumor formation, and mortality associated therewith, in 6‐day‐old NMRI mice inoculated intracerebrally with Moloney murine sarcoma virus (MSV). Even at a dose as low as I mg/kg/day, PMEA effected a significant delay in tumor formation. When evaluated in parallel with PMEA, 3′‐azido‐2′,3′‐dideoxythymidine (AZT) conferred a comparable tumor‐inhibitory effect at a 5‐ to 10‐fold higher dose than PMEA. Prolonged treatment of MSV‐infected mice with PMEA resulted in long‐term survivors without apparent signs of tumor development. In view of the propensity of HIV to spread to the central nervous system (CNS), the marked activity shown by PMEA against experimental retrovirus infection of the brain in mice points to its potential in the treatment of AIDS and other retrovirus infections of the CNS.
Epstein‐barr virus internalization and infectivity are blocked by selective protein kinase C inhibitors
Authors: Cirone Mara , Angeloni Antonio , Barile Giuseppe , Zompetta Claudia , Venanzoni Marco , Torrisi Maria Rosaria , Frati Luigi , Faggioni Alberto
Published: February 2007

Selective protein kinase C inhibitors can either block or significantly reduce Epstein‐Barr virus infectivity: inhibition of transformation and decreased 3H‐thymidine (3H‐TdR) incorporation in human B lymphocytes infected with B95‐8 EBV, as well as a significant reduction in the induction of early antigens in Raji cells superinfected by P3HRI EBV was achieved by pre‐treating the cells with the inhibitors. The inhibitors do not act by blocking binding of the virus to its cellular receptor CR 2, but rather are effective in the viral internalization process. Our results suggest that protein kinase C may be involved in the process of viral entry into cells.