bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiologic evidence of an association between body iron stores and risk of cancer
Authors: Selby Joseph V. , Friedman Gary D.
Published: February 2007

Biologic evidence suggests that high body iron stores could promote development of cancer. Because a previous study had shown an association between prescribed iron medication and lung cancer risk in men, we examined recent iron use as well as 2 additional indirect measures of body iron stores, anemia and the total iron‐binding capacity (TIBC) of plasma, in relation to subsequent risk of cancer in a larger cohort of 174,507 persons. Women, but not men, who reported recent iron use had a lower risk of lung cancer Chan those who did not [RR = 0.60, 95% confidence limits (CL) 0.37, 0.97] after adjustment for age and cigarette smoking. Women who had used iron appeared to remain relatively iron‐depleted. Risk for other cancers was slightly, but not significantly, lower in women who used iron. Anemia (hemoglobin < 12 g) was also associated with lower risk of lung cancer in women (RR = 0.61, 95% CL 0.61, 0.98), but not in men. TIBC, which is inversely related to body iron stores, was inversely related to risk of lung cancer in women in a graded fashion (RR = 0.41, 95% CL 0.23, 0.73 comparing highest with lowest quartile). In men, a protective effect of higher TIBC against lung cancer was suggested, but did not reach statistical significance. These indirect measures of body iron stores appeared to reflect iron stores better in women than in men, probably because variability in iron stores is greater in women and iron deficiency more prevalent. A possible alternative explanation for our findings is incomplete adjustment for the confounding effects of cigarette smoking. This could apply to iron use and hemoglobin level which were related to smoking, but not to TIBC, which was nat. These data, which indicate lower risk of cancer in iron‐depleted women, lend epidemiologic support to the hypothesis that high iron stores may increase cancer risk, at least for lung cancer.
Ectopic expression of the Y (Ley) antigen defined by monoclonal antibody 12‐4LE in distal colonic adenocarcinomas
Authors: Bara Jacques , Mollicone Rosella , Herrero‐Zabaleta Eugenie , Gautier Rodolphe , Daher Nagib , Oriol Rafael
Published: February 2007

Monoclonal antibody (MAb) 12‐4LE reacts specifically with the αFuc(1‐2)βGal(1‐4)[αFuc(1‐3)]GlcNAc‐R synthetic oligosaccharide and consequently characterizes the Y (Ley) antigen. In normal individuals, this MAb reacts more strongly on samples from blood group O persons, indicating that the Y structure is better recognized when terminal A or B sugars are not added to the Y structure. In fetal and normal adult gastrointestinal tract, this antibody reacts with the epithelium of stomach, small intestine and proximal colon, but not of distal colon. In the adult, cells from the surface epithelium of the gastric, small intestinal and cecal mucosae express the Y antigen according to the secretor phenotype of each individual, thus characterizing the so‐called “upward differentiation” pattern. In contrast, mucus cells of the pylorus and duodenal Brünner glands, as well as Paneth cells, always express the Y antigen irrespective of secretor phenotype, thereby characterizing the so‐called “downward differentiation” pattern. Proximal fetal colonic mucosa has the same genetic control as the downward differentiation pattern of the adult. Distal fetal colonic mucosa is negative with anti‐Y, as in the adult. Y antigen was not expressed in hyperplastic (10 cases), juvenile (5 cases) or adenomatous (42 cases) polyps, except for some spreading villous adenomas in which rare Y‐positive foci could be observed but which were not specifically associated with dysplastic glands. Polyps from familiar polyposis did not express this antigen. In adenocarcinomas, the Y antigen was expressed in 41/45 (91%) of distal tumors and 15/35 (43%) of cecal tumors, independently of ABO phenotype. The ectopic expression of this Y antigen on distal colon adenocarcinomas may be a useful tool in the detection of distal colonic carcinomas.
Syngeneic in vivo passage of the murine BW 5147 lymphoma results in the expression of a stable metastatic phenotype
Authors: De Baetselier Patrick , Roos Ed , van Hecke Dominique , Verschaeve Luc , Brys Lea , Verschueren Hendrik
Published: February 2007

BW 5147 lymphoma tells are non‐invasive tumor cells which do not generate experimental m etas Cases following i.v. inoculation. In contrast, s.c. and intra‐splenic (i.s.) growth of BW cells resulted in widespread colonization of liver and spleen. Cells derived from either s.c. tumors or metastatic lesions did generate metastases after i.v. administration. The capacity of these tumor‐derived BW cells to disseminate via blood‐borne cells was irreversible and stable, indicating that one in vivo passage of BW cells results in the generation of new, metastatic BW variants. Concomitantly, these variants exhibited an inherent invasive potential as manifested by their capacity to infiltrate in vitro monolayers of hepatocytes and fibro‐blasts. The BW variants expressed new membrane markers such as H‐2 antigens, the Lyt 1,2 T‐cell differentiation antigen and the MTH antigen (a newly defined membrane antigen, expressed predominantly on murine metastatic T‐cell lymphomas and mature T lymphocytes). This phenomenon was observed with both cloned and uncloned BW populations, suggesting that an inductive rather than a selective mechanism accounts for the transition of BW cells towards a more malignant phenotype. These observations confirm the concept that local factors at the growth site of a tumor might influence the metastatic behavior of that tumor, possibly via induction of silent differentiation programs.
Albumin‐negative hepatocytes in sprague‐dawley x analbuminemic F1 rats treated with hepatic carcinogens
Authors: Ogawa Katsuhiro , Yokota Kin‐Ichi , Sonoda Tomoko , Piao Zhi Si , Mori Michio , Nagase Sumi
Published: February 2007

Analbuminemic rats (NAR) are a mutant breed with an inherent inability to synthesize albumin. However, heterozygous rats born of a pair of NAR and Sprague‐Dawley (SD) rats can synthesize albumin. Immunohistochemical staining for albumin shows that, although the majority of hepatocytes of SD x NAR F1 (female SD x male NAR) rats are positive for albumin, a small number of hepatocytes are negative. These albumin‐negative hepatocytes are frequently found in the form of clusters which appear cytologically normal. When the rats were given a dietary regimen of 2‐acetyl‐aminofluorene (2‐AAF), there was a significant increase in the number of albumin‐negative hepatocytes. On the other hand, diethylni‐trosamine (DEN) or 5‐azacytidine did not increase the number of albumin‐negative hepatocytes. 2‐AAF and DEN also induced enzyme‐altered hepatocytes but the albumin‐negative hepatocytes were of a completely different class from the enzyme‐altered hepatocytes. The results of this study indicate that some kind(s) of carcinogens induce mutated hepatocytes which are probably not involved in carcinogenesis.
Both N‐ras and c‐myc are activated in the shac human stomach fibrosarcoma cell line
Authors: Andeol Y. , Nakdeux P. C. , Daya‐Grosjean L. , Brison O. , Cebrian J. , Suarez H.
Published: February 2007

A transforming N‐ras gene was isolated from the SHAC human stomach fibrosarcoma cell line. A single‐point mutation resulting in the substitution of histidine for glutamine at codon 61 was found in the SHAC transforming allele. The N‐ras gene is overexpressed in the tumor cells and transformant cells. The N‐ras p21 product was studied by immunoprecipi‐tation and showed no alteration in mobility as compared to the normal p31 protein. The c‐myc gene is amplified and overexpressed in these cells. This report gives evidence that an amplified c‐myc and a mutated N‐ras gene are both present in this tumor cell line and provides support for the idea that co‐operation of at least 2 activated cellular oncogenes is required for carcinogenesis.
Three epstein‐barr virus (EBV)‐determined nuclear antigens induced by the BamHI E region of EBV DNA
Authors: Shimizu Norio , Yamaki Mitsuo , Sakuma Sadatoshi , Ono Yasushi , Takada Kenzo
Published: February 2007

In our previous study (Takada et al., 1986a), we showed that the BamHI E fragment of Epstein‐Barr virus (EBV) DNA induces a nuclear antigen that is detected by human antisera against EBV‐determined nuclear antigen (EBNA), when transfected into baby hamster kidney (BHK) cells. The present study shows that the sub‐fragment containing the central open reading frame BERF2b of the BamHI E fragment (Baer et al., 1984) is responsible for nuclear antigen induction. In addition, 2 fragments corresponding to 2 other open reading frames of the BamHI E, BERF1 and BERF4 also induce nuclear antigens upon transfection into BHK cells. These 3 antigens, designated RF2b, RF1 and RF4 antigens, were serologically classified as EBNA and andgenically distinct. In immunoblotting analysis of latently EBV‐infected BJ‐B95‐8 cells, 3 high‐molecular‐weight polypeptides (136, 142 and 147 kDa) ware identified by anti‐EBNA sera. Immunoblotting analysis of transfected BHK cells indicated that the RF2b antigen is 145 kDa in its native form and antigenically related to the 147‐kDa protein of BJ‐B95‐B cells. Although RF1 and RF4 antigens were not detected by immunoblotting, reactivities of sera with RF1 and RF4 antigens in the immunofluorescence test were correlated with those of sera with the 136‐ and 142‐kDa polypeptides of BJ‐B95‐8 cells, respectively. The results suggest that 3 high‐molecular‐weight proteins of latently EBV‐infected cells are encoded by 3 open reading frames of the BamHI E DNA fragment.
Variants of amphotropic type‐C retrovirus isolated from cultures of moloney‐ and rauscher‐MuLV‐induced tumors
Authors: Chang Kenneth S. S. , Wang Lai‐Che , Gao Changlie
Published: February 2007

We isolated and characterized 2 strains of type‐C retrovirus, R5NX and YACNX, from established lymphoid cell cultures derived from Rauscher‐MuLV‐induced lymphoma (RBL‐5) in a C57BL/6 mouse, and Moloney‐MuLV‐induced lymphoma (YAC) in an A‐strain mouse, respectively. The RSNX and YACNX viruses were compared with the prototype 4070A strain of amphotropic virus isolated from feral mice in California, and were found to belong to the same amphotropic virus class on the basis of viral interference, neutralization tests, and other biological properties. However, they were not quite identical with respect to viral neutralization antigens and restriction enzyme cleavage patterns of the proviral DNA. The possibility that these viruses may have been present in the original tumor together with the R‐MuLV or M‐MuLV as “exogenous” viruses rather than as contaminants of cell cultures by the 4070A virus is discussed. Although these 1 new isolates were not pathogenic when inoculated into newborn C3H/HE mice, they could establish persistent infections in these mice.
Enzymatic elimination of O6‐ethylguanine from the DNA of ethylnitrosourea‐exposed normal and malignant rat brain cells grown under cell culture versus in vivo conditions
Authors: Huh Nam‐Ho , Rajewsky Manfred F.
Published: February 2007

The developing rat brain exhibits a pronounced susceptibility to the tumorigenic effect of ethylnitrosourea (EtNU) and an extremely low repair activity for the DNA alkylation product O6‐ethylguanine (O6‐EtGuar‐). We have recently found that a collection of malignant neural cell lines originating from prenatal BDIX‐rat brain cells were all highly O6‐EtGua repair‐proficient (O6‐EtGuar+). Subcloned lines showed considerable variability of the repair capacity, suggesting instability of the O6‐EtGua repair phenotype. Using one of the subcloned lines (BT3Caf) as a model, we show here that BT3Caf cells grown in monolayer culture repair O6‐EtGua much more rapidly than those grown in the form of s.c. tumors in BDIX‐rats (whereas O6‐ethylthymine is not repaired under either condition). Furthermore, normal prenatal BDIX‐rat brain cells (O6‐EtGuar‐ in vivo) gradually acquire an O6‐EtGuar‐ phenotype upon transfer to long‐term monolayer culture. The cellular capacity for enzymatic DNA repair is of particular relevance in relation to both the malignant transformation of normal cells and the therapeutic inactivatton of cancer cells by DNA‐reactive drugs. Further analyses are thus required of the molecular mechanisms controlling the expression of DNA repair enzymes as a function of cell differentiation, in terms of the cellular response to altered microenv iron mental conditions, and in search for possibilities to reduce the repair capacity of cancer cells.
High tumour prolactin receptor content and lack of increase in serum prolactin levels as predictors of good response to endocrine therapy in rat mammary cancer
Authors: di Carlo F. , Muccioli G. , Bellussi G. , Conti G. , Racca S.
Published: February 2007

Correlations between anti‐neoplastic activity of medroxy‐progesterone acetate (MPA), on the one hand, and serum prolactin (PRL) levels as well as tumour PRL and insulin receptor content, on the other, were investigated in female rats bearing dimethylbenzanthracene (DMBA)‐induced mammary tumours. Changes in liver PRL receptor concentrations were also studied. MPA was injected for 15 days. Regression was observed in 16 out of 50 (32%) tumours from rats treated with MPA. Twenty‐seven out of 50 (54%) continued to grow regardless of treatment. Stasis was seen in the remaining 7 tumours (14%). Serum PRL levels increased significantly in rats with tumours which were non‐responsive to MPA. Concentration of PRL receptors in the liver of all animals was reduced by MPA treatment. A remarkable increase occurred only in those mammary tumours which responded to therapy. The concentrations of PRL receptors in the tumours non‐responsive to MPA were similar to those detected in control tumours. Unlike PRL receptors, tumour insulin receptor levels were not modified by MPA treatment, five out of 14 tumours (35.7%), previously growing in spite of MPA administration, regressed when bromocriptine was added to MPA. A significant reduction in serum PRL levels occurred in all rats undergoing the latter treatment. No difference was observed between responsive and non‐responsive animals; on the contrary, the PRL receptor content of responsive tumours increased significantly in comparison with that of non‐responsive tumours.
Analysis of integrated hepatitis B virus DNA and cellular flanking sequences cloned from a hepatocellular carcinoma
Authors: Matsumoto Hisashi , Yoneyama Tetsuo , Mitamura Keiji , Osuga Toshiaki , Shimojo Hiroto , Miyamura Tatsuo
Published: February 2007

By digestion with HindIII restriction enzyme, a human hepatocellular carcinoma was shown to contain only 2 hepatitis B virus (HBV) DNA inserts. Both HindIII fragments (8 and 16 kb) were molecularly cloned and the structures of HBV DNA and adjacent host sequences were analyzed. One clone λYH 8) contained part of pre‐S(I) through the entire S gene and the other (λYH 16) had the middle section of the S to the end of X gene of HBV DNA. No gross rearrangements were observed in either HBV or cellular DNA sequences in λYH 16 clone. However, the 8 kb HindIII fragment was considered to be amplified together with flanking cellular sequences. Furthermore, the HBV DNA was integrated into cellular genome at the Alu repeated sequences in λYH 8.
Expression of the c‐fgr related transcripts in epstein‐barr virus‐associated malignancies
Authors: Klein Christine , Busson Pierre , Tursz Thomas , Young Lawrence S. , Raab‐Traub Nancy
Published: February 2007

The proto‐oncogene c‐fgr is expressed at high levels in cell lines derived from lymphomas which are infected with Epstein‐Barr virus (EBV) (Cheah et al., 1986). mRNA extracted directly from biopsies of EBV‐infected tissues was analyzed on Northern blots to determine if c‐fgr is expressed during lympho‐proliferations induced in vivo by EBV and in nasopharyngeal carcinoma (NPC), the epithelial malignancy associated with the virus. Elevated levels of c‐fgr expression were detected in all EBV‐positive lympho‐proliferations in vivo but not in cell lines established by EBV infection in vitro. This indicates that the induction of the c‐fgr proto‐oncogene is not an essential component of EBV‐induced transformation. Although no c‐fgr expression was detected in EBV‐positive or ‐negative epithelial cell lines, the 3.0‐kb c‐fgr mRNA was detected at low levels in mRNA obtained from NPC biopsy specimens. However, NPC tissue, after passage in nude mice (which eliminates infiltrating lymphoid and myeloid cells) did not contain the 3.0‐kb c‐fgr mRNA. The absence of expression of c‐fgr in the malignant epithelial cells infected with EBV contrasts with the elevated level of the proto‐oncogene in EBV‐infected lymphoma tissue and cell lines established from lymphomas. This suggests differences in the expression of cellular functions in EBV‐induced malignancies of these 2 distinct cell types.
Use of syngeneic monoclonal antibodies in the therapy of disseminated myeloid leukemic cells
Authors: Berends D. , Mulder A. H. , van Houwelingen G. , de Both N. J.
Published: February 2007

A syngeneic monoclonal antibody (MAb) (IC5F5) was successfully used in the immunotherapy of Rauscher‐virus‐induced myeloid leukemic RMB‐1 cells. It is directed to a virus‐encoded, but aberrantly processed protein, which is expressed on the cell membrane. When applied in vivo, it binds only to RMB‐1 tumor cells. BALB/c mice were inoculated i.p. or i.v. with 107 RMB‐1 cells and died within 2–3 weeks due to increasing tumor load. Mice inoculated i.p. were completely cured by daily injections of ascites containing IC5F5. Disseminated tumor cells in liver and hemopoietic organs were observed after i.v. inoculation. Daily treatment with MAbs resulted in survival beyond 90 days. No antigenic modulation was observed when tumor tissue was analyzed 2–10 days after treatment. Treatment was successful even when therapy was postponed until day 5 following inoculation of tumor cells. When the number of ascites injections was reduced, survival was identical to that observed among repeatedly treated mice. Ten‐ and 100‐fold dilution of ascites fluid diminished the number of survivors, but still resulted in a median survival time of 38 and 20 days, respectively, as compared to 14 days for untreated mice.
Mast‐cell‐deficient W/Wv mice exhibit A decreased rate of tumor angiogenesis
Authors: Starkey Jean R. , Crowle Patricia K. , Taubenberger Simone
Published: February 2007

The role of host mast cells in tumor‐associated angiogenesis was investigated by comparing the angiogenic response of genetically mast‐cell‐deficient W/Wv mice and mast‐cell‐sufficient +/+ littermate mice to s.c. growing B16‐BL6 tumors. The angiogenic response was found to be slower and initially less intense in W/Wv mice than in +/+ mice. Fewer W/Wv mice than +/+ mice developed spontaneous lung metastases and W/Wv mice exhibited fewer lung metastases per mouse. Bone‐marrow repair of the mast‐cell deficiency restored the angiogenic response of W/Wv mice and also restored the incidence of hematogenous metastases to approach that of +/+ mice. Differences in lymphatic metastasis were not detected between W/Wv and +/+ mice. These results demonstrate a role for mast cells in vivo during tumor angiogenesis, and suggest a role also for host mast cells in hematogenous metastasis.
Correlation between urokinase‐type plasminogen activator production and the metastasizing ability of two murine mammary adenocarcinomas
Authors: Pereyra‐Alfonso Susana , Haedo Ana , de Kier Joffe Elisa Bal
Published: February 2007

Plasminogen activator (PA) activity was studied in a transplantable murine mammary adenocarcinoma (M3), moderately metastatic to lungs, and in a highly metastatic variant tumor (MM3) to establish whether a correlation existed between this enzyme and the tumors' metastasizing abilities. The cell‐associated and secreted PA activities from primary cultures of both tumors, as well as from solid tumor homogenates, were quantitated by means of a fibrinolytic assay. Immunoneutralization and zymographic assays were done to identify the PA present in both tumors. In culture, the highly metastasizing MM3 cells produced (secreted plus cell‐associated activator) 3.3‐fold higher PA levels than the M3 cells. This difference was mainly attributed to the enhanced secreting ability of MM3, as these tumor cells secreted 102 times their cell‐associated PA activity within 24 hr, while M3 cells secreted only 11 times this activity during the same period. PA activity was also significantly higher in MM3 than in M3 tumor homogenates. Acid‐labile inhibitors and non‐specific proteases were not detected. In both tumors, PA was characterized as urokinase‐type, with a molecular weight of approximately 48 kDa. These results suggest that, in this model, PA plays a role in metastasis formation.
Alterations in c‐myc expression in relation to maturational status of human colon carcinoma cells
Authors: Mulder Kathleen M. , Brattain Michael G.
Published: February 2007

Previous work from this laboratory established a large bank of human colon carcinoma cell lines in culture and classified them with respect to growth regulatory phenotypes based on several biological and biochemical characteristics. In the present report, Northern analysis indicates that addition of the maturational agent N,N‐dimethylformamide (DMF) (1.0%) to proliferating HCT 116 and MOSER cells resulted in a repression of c‐myc proto‐oncogene expression; retinoic acid (1.0 μM) was less effective in this regard. Repression of c‐myc expression by DMF was observed in MOSER and HCT 116 cells, whether it was added to proliferating or late log phase cultures, and was associated with a corresponding reduction in cellular proliferation. The reduction in c‐myc expression by DMF did not require new protein synthesis and occurred within a few minutes after its addition, resulting in a 70% reduction within approximately 2 hr. Previous work from this laboratory indicated that transforming growth factor‐β (TGF‐β) elicited alterations in MOSER cells similar to those observed following DMF treatment. The present report demonstrates that proliferating, but not late log phase, MOSER cells responded to TGF‐β with a repression of c‐myc expression. Similarly, an inhibition of cellular proliferation was only observed when TGF‐β (10 ng/ml) was added to proliferating cells. Collectively, these findings indicate that repression of c‐myc expression is associated with diminished cellular proliferation and the induction of a more benign phenotype in human colon carcinoma cells. Furthermore, this report is the first demonstration of a c‐myc response to TGF‐β in an epithelial cell line.
Effect of retinoic acid on bovine papillomavirus (BPV) DNA‐induced transformation and number of BPV DNA copies
Authors: Tsang Siu Sing , Li Gang , Stich Hans F.
Published: February 2007

The effect of all‐trans‐retinoic acid (RA) was examined on (1) transformation induced in C127 cells by transfection with plasmid pdBPV‐1 (142‐6), which contains DNA of bovine papillomavirus (BPV), (2) the capacity of transformed BPV DNA‐containing clones to form colonies with transformed properties (e.g., piling up into multilayered colonies), and (3) the number of BPV DNA copies in transformed cells. At nontoxic doses ranging from 10−7 to 10−5M, RA reduced the frequency of transformed foci in a dose‐dependent manner. The extent of inhibition depended on the length of RA treatment and on the time that elapsed between DNA transfection and RA treatment. RA exerted only a slight inhibitory effect during the first days after transfection. Complete inhibition was observed when the cells were continuously exposed after transfection to RA at doses ranging from 0.5 to 1 × 10−5M. The inhibitory effect of RA on transformation was reversible. Transformed foci started to form after withdrawal of RA treatment. In the presence of RA (5 × 10−6M), cells from transformed colonies were no longer able to form foci displaying transformed properties. The number of BPV DNA copies gradually decreased when the cells were grown over several generations in the presence of RA (5 × 10−6M). After approximately 30 cell generations, the cell cultures appeared to have less than one copy of BPV DNA.
New cell line from hairy‐cell leukemia: Confirmation of leukemic cell origin by karyotype and IG gene analysis
Authors: Tokumine Yukihiro , Ueda Etsuko , Ogawa Hiroyasu , Sugiyama Haruo , Taniwaki Masafumi , Abe Tatsuo , Kanayama Yoshio , Hashimoto Tomoko , Inoue Ryoichi , Machii Takashi , Kitani Teruo
Published: February 2007

A hairy‐cell leukemia (HCL) line, BNBH‐1, was established from the peripheral blood of a 40‐year‐old male patient with HCL in a relatively stable clinical phase after splenectomy. The cells have since been growing continuously for more than 2 years. Their cell surface immunoglobulin (slg) was identical with that found on the surface of freshly isolated leukemic cells, consisting of IgG‐K. The BNBH‐1 cells were more mature than the original hairy cells in their degree of B‐cell differentiation, as reflected by a decrease in slg expression together with the appearance of some cytoplasmic lg (clg)+ cells, loss of EAγ‐rosette formation and reactivity with monoclonal antibody (MAb) FMC7, and an increase in the proportion of MAb PCA‐1+ cells. The BNBH‐1 cells possessed the antigen recognized by Leu‐MS, a highly specific MAb for HCL. Epstein‐Barr virus nuclear antigen (EBNA) was present. Both the freshly isolated leukemic cells and the cell line had the 14q + involving q32 chromosomal abnormality, and their lg gene rearrangements were also identical. Following exposure to 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), both the freshly isolated leukemic cells and the BNBH‐1 cells adhered to culture dishes and extended long, thin processes, a phenomenon characteristic of HCL. These results indicate that the BNBH‐1 line was derived from the leukemic hairy cells.
Characterization of a human ovarian carcinoma cell line, OTN 14, derived from a mucinous cystadenocarcinoma
Authors: van Niekerk C. C. , Poels L. G. , Jap P. H. K. , Smeets D. F. C. M. , Thomas C. M. G. , Ramaekers F. C. S. , Vooijs G. P.
Published: February 2007

A human ovarian carcinoma cell line, OTN 14, has been established from malignant ascitic fluid of a patient with a well‐differentiated mucinous cystadenocarcinoma of the left ovary. The cell line has been maintained in vitro for 6 months through 23 passages, growing in monolayers as well as in 3‐dimensional clusters, with a population doubling time of 281/2 hr. The number of chromosomes per cell varied from 67 to 88, with a modal number of 86. Two characteristic marker chromosomes were recognized, consisting of partially deleted chromosome I. With a DNA index of 1.934 the tumour cell line was near tetraploid. The epithelial character of the OTN 14 cells was confirmed by a positive immunofluorescence reaction with monoclonal antibodies (MAbs) against different keratins, and when (immuno)electron microscopy was used, keratin filaments and small junctional complexes were observed. Vimentin was also expressed in these cells, while desmin was not detected. Cultured tumour cells reacted (weakly) positive with MAb OV‐TL 3 as a marker for ovarian carcinomas, while reactivity with the anti‐ovarian carcinoma MAb OC 125 was limited to a few cells, not permitting the detection of shed CA 125 antigen in the culture supernatant. Cells stained heterogeneously positive for CEA marker BW 431/31, the presence of which was confirmed by detection of CEA shed into the culture medium. The cell line released estradiol at a concentration of 130,000 pmol/L in the culture medium, while no progesterone or dehydroepiandrosterone sulphate were found. Electron microscopical evidence for steroid production was suggested in some cells showing “dense‐core” vesicles near the Golgi areas. The OTN 14 tumour cells formed poorly differentiated tumour nodules in nude mice, and metastatic cells were also found in blood capillaries. Cell types with mucinous as well as endocrine characteristics were found.
Syngeneic monoclonal antibodies directed against rauscher virusinduced myeloid leukemic cells: Isolation and characterization
Authors: Berends D. , Rhijnsburger E. H. , van Gaalen J. L. M. , van Houwelingen G. , Zondervan P. E. , de Both N. J.
Published: February 2007

Hybridomas producing syngeneic monoclonal antibodies (MAbs) were prepared by fusion of spleen cells of BALB/c mice, which were immunized with sublethal doses of RMB‐1 cells. This cell line originates from a Rauscher virus (R‐MuLV)‐induced myeloid leukemia and forms tumors when re‐inoculated into mice. MAbs were characterized as regards their reactivity against virally and non‐virally induced cell lines. Two selected MAbs, ICSF5 and 4D2B4, were analyzed further. Their binding to subcellular structures was determined, and so were the properties of the antigens to which they are directed. MAb IC5F5 is of the IgG2A and 4D2B4 of the IgG2b subclass. Both bind to R‐MuLV‐infected or ‐transformed cell lines and are not mutually competitive. The antibodies do not react with other murine and human myeloid leukemic cells. As shown by immuno‐electron microscopy, these MAbs have affinity to the cell membrane of non‐virus producing RMB‐1 cells. When lysates of purified virus were analyzed, the MAbs were found to be directed to the gag precursor protein Pr65, and one of them (IC5F5) also to be directed to the core protein p12. In RMB‐1 cells, binding occurs to a 50‐kDa glycoprotein and 2 proteins of 26 and 29 kDa. Since RMB‐1 cells do not produce virus, but express aberrant viral proteins, these MAbs are tumor‐specific and useful for immunotherapy.
Anti‐tumor effects of tumor necrosis factor alone or combined with radiotherapy
Authors: Sersa Gregor , Willingham Veronica , Milas Luka
Published: February 2007

Recombinant human tumor necrosis factor (rHuTNF) was investigated for its ability to increase the response of murine tumors to ionizing radiation. Both multiple i.v. administrations of rHuTNF and local tumor irradiation caused a significant delay in tumor growth. The effect of treatment with both agents combined was greater than the additive effect of the individual treatments. Furthermore, rHuTNF significantly increased tumor radiocurability, as assessed by the TCD50 assay. rHuTNF was not cytotoxic to tumor cells, nor did it affect their radiosensitivity. The in vivo anti‐tumor effect of rHuTNF and its augmentation of tumor radioresponse were mediated through indirect mechanisms, either immunological or non‐immunological. rHuTNF was also effective in reducing the damaging effect of ionizing radiation on bone‐marrow progenitor cells, which could increase the therapeutic advantage of the rHuTNF‐radiotherapy combination. These experiments suggest that rHuTNF is potentially beneficial in combination with radiotherapy.
Monoclonal antibody mapping of keratins 8 and 17 and of vimentin in normal human mammary gland, benign tumors, dysplasias and breast cancer
Authors: Guelstein V. I. , Tchypysheva T. A. , Ermilova V. D. , Litvinova L. V. , Troyanovsky S. M. , Bannikov G. A.
Published: February 2007

The distribution of keratins 8 and 17 and of vimentin in 28 normal human mammary tissue samples, 16 benign tumors, 26 fibrocytic diseases and 52 malignant breast tumors have been studied using monoclonal antibodies H1, E3 and NT30, respectively. Three cell populations in normal mammary epithelium have been identified: luminal epithelium containing keratin 8, myoepithelium of the lobular structures positive for vimentin, and myoeplthelium of extralobular ducts positive for keratin 17. In different kinds of benign tumor and dysplastic proliferation a mosaic of cells with all normal phenotypes has been observed. The majority of cells co‐expressed keratins 8 and 17 or vimentin. In the overwhelming majority of carcinomas, cells did not contain myoepithelial markers (keratin 17 and vimentin) but expressed only keratin 8 specific to normal luminal epithelium.
Case‐control study of proximal and distal colon cancer and diet in Wisconsin
Authors: Young Theresa B. , Wolf Dennis A.
Published: February 2007

The relationship between diet and subsite‐specific colon cancer was investigated using dietary histories obtained from a statewide, population‐based sample of 152 proximal colon cancer patients, 201 distal colon cancer patients and 618 general population controls. The results do not support hypotheses that (1) dietary fat and cholesterol are more strongly related to proximal colon cancer and (2) vegetables and other dietary sources of fiber are more strongly associated with distal colon cancer. Vegetable consumption over lifetime was consistently protective for both proximal and distal colon cancer. Odds ratios and 95% confidence intervals for the most significant dietary factors (based on high vs. low consumption) for proximal colon cancer were: salad, 0.29 (0.17, 0.48); miscellaneous vegtables, 0.58 (0.35, 0.97); cruciferous vegetables, 0.59 (0.35, 0.97); processed lunchmeat, 2.04 (1.31, 3.17); panfried foods, 1.79 (1.15, 2.80); eggs, 1.75 (1.02, 2.99) and for distal colon cancer they were: salad, 0.43 (0.28, 0.67); cruciferous vegetables, 0.44 (0.28, 0.71); cheese, 0.62 (0.40, 0.96); processed lunchmeat, 1.79 (1.17, 2.73); pan‐fried foods, 1.55 (1.03, 1.27). The results support recommendations that the “prudent diet” (low‐fat, high‐vegetable) may reduce colon cancer risk.
Prognostic value of ebv markers in the clinical management of nasopharyngeal carcinoma (NPC): A multicenter follow‐up study
Authors: De‐Vathaire F. , Sancho‐Garner H. , De‐Thé H. , Pieddeloup C. , Schwaab G. , Ho J. H. C. , Ellouz R. , Micheau C. , Cammoun M. , Cachin Y. , De‐Thé G.
Published: February 2007

Between December 1979 and April 1982, 373 patients with untreated, undifferentiated carcinoma of the nasopharynx (NPC), 99 in Hong Kong, 120 in Tunis and 154 in Villejuif, entered a longitudinal study aimed at determining the clinical prognostic value of EBV serology after radiotherapy. A minimum of 3 years' follow‐up was achieved for 319 patients (83 in Tunis, 95 in Hong Kong and 141 in Villejuif) who had regular clinical and serological testing at intervals of 6–8 months. No significant difference in initial serology (i. e., before any treatment) or variations of antibody titers at time of first followup was observed between patients who achieved complete remission after radiotherapy and those who did not. This included IgG and IgA antibodies to VCA, EA or EBNA. However, when patients with confirmed clinical remission I year after completion of radiotherapy were studied, the value of IgG/EA and mainly of IgA/EA increasing titers became highly significant for prediction of relapse, regardless of the initial titers. This demonstrated the clinical usefulness of EBV serology for NPC patients who have confirmed clinical remission after radiotherapy.
Monoclonal antibodies produced by immunization with neoglycoproteins containing galα1‐4galβ1‐4glcβ‐O and galα1‐4galβ1‐4glcnacβ‐O residues: Useful immunochemical and cytochemical reagents for blood group p antigens and a differentiation marker in burkitt lymphoma and other B‐cell malignancies
Authors: Brodin N. Thomas , Dahmén Jan , Nilsson Bertil , Messeter Lisbeth , Mårtensson Stig , Heldrup Jesper , Sjögren Hans Olov , Lundblad Arne
Published: February 2007

Several monoclonal antibodies (MAbs) directed to blood group P1 (Galα1‐4Galβ1‐4GlcNAcβ‐O) and Pk (Galα1‐4Galβ1‐4Glcβ‐O) determinants were produced with high efficiency by using synthetic neoglycoproteins as immunogens. The specificity of IgM and IgGI MAbs was characterized by binding to defined oligosaccharides and glycoconjugates. Antibodies that bound equally well to P1 and Pk determinants and to Galαl‐4Galβ1‐O‐derivatives were obtained, together with others that showed selective recognition of the entire trisaccharide chain. Selected antibodies were shown to be useful as reagents for detection of the blood group P antigens in glycolipid extracts of erythrocytes and on the surface of erythrocytes of different P phenotypes, demonstrated both by radioimmune assays and hemagglutination. Six IgM MAbs directed to the Pk determinant bound selectively to Burkitt lymphoma cells and 2 of these antibodies (424/3D9 and 424/6A2) could be used as auxiliary reagents in immunofluorescence for diagnosis and classification of B‐cell lymphomas and leukemias using flow cytometric analysis. Eight normal individuals and 37 patients with lymphoma or leukemia were studied. Tumor cells of 2/2 patients with “Burkitt‐like” lymphoma, 1 patient with centroblastic lymphoma and 2 patients with acute leukemia were strongly stained for the Pk antigen. The staining patterns for differentiation markers classified the tumor cells to a developmental stage closely related to the Burkitt cell type.
Remission of oral leukoplakias and micronuclei in tobacco/betel quid chewers treated with beta‐carotene and with beta‐carotene plus vitamin A
Authors: Stich Hans F. , Rosin Miriam P. , Hornby A. Paul , Mathew Babu , Sankaranarayanan R. , Nair M. Krishnan
Published: February 2007

Fishermen from Kerala (India) who chewed tobacco‐containing betel quids daily (17.2 ± 9.6 quids per day) and had well‐developed oral leukoplakias with elevated frequencies of micronucleated cells participated in a short‐term intervention trial. Beta‐carotene (180 mg/week) (Group I), beta‐carotene (180 mg/week) plus vitamin A (100,000 IU/week) (Group II), and placebo (Group III) capsules were given twice weekly for 6 months under strict supervision. The remission of oral leukoplakias, the inhibition of new leukoplakias, and the reduction of micronucleated oral mucosal cells were recorded at the 3rd and 6th months of the trial period. After 3 months, the frequency of micronucleated cells was significantly reduced in Group I (from 4.09% to 1.1% in areas of leukoplakia, and from 4.1% to 1.0% in the normal mucosa). At this time, remission of oral leukoplakias did not differ significantly from that observed in the placebo group. After 6 months of treatment, remission of leukoplakias in Group I (14.8%) and Group II (27.5%) differed significantly from that seen in Group III (3.0%). The development of new leukoplakias during the 6 months period was strongly inhibited in Group II (7.8%), and to a lesser degree in Group I (14.8%), as compared to Group III (21.2%). During the trial period, all participants continued to chew tobacco‐containing betel quids in their accustomed manner. Thus, remission and inhibition of new oral leukoplakias and reduction of micronucleated mucosal cells occurred in the groups receiving beta‐carotene and beta‐carotene plus vitamin A during the continuous presence of carcinogens derived from tobacco and areca nut.
The Danish case‐control study of cutaneous malignant melanoma. I. Importance of host factors
Authors: Østerlind A. , Tucker M. A. , Hou‐Jensen K. , Stone B. J. , Engholm G. , Jensen O. M.
Published: February 2007

The relationshop between cutaneous malignant melanoma and possible host factors was Investigated in a populationbased case‐control study from East Denmark over a 3‐year period. A total of 474 melanoma patlents and 926 population controls aged 20–79 years were interviewed. Patients with lentigo maligna melanoma were not included. The major constitutional risk factors were: number of raised naevi on the arms (RR = 5,1 for 5+ vs, none), degree of freckling (RR = 2.9 for many vs, none), and light hair colour (RR = 1.7 for blond/fair vs. dark brown/black), which were independent of one another. An apparent synergy between number of raised naevi on the arms and degree of freckling was found. Thus, persons at high risk of melanoma may be identified by a simple assessment of naevi and degree of freckling. No significent difference was found between superficial spreading melanoma and nodular melanoma with regard to the most important host factors.
Immunolocalization of an angiogenic factor (HAF) in normal, inflammatory and tumor tissues
Authors: Fröhbeis Bärbel , Zwadlo Gabriele , Broöcker Eva‐Bettina , Osthoff Klaus Schulze , Hagemeier Hana‐Hermann , Topoll Heinrich , Sorg Clemenns
Published: February 2007

The distribution of a novel human angiogenic factor (HAF) (Schulze Ostoff et al., 1987) has been investlgated on various human cell lines, isolated blood cells as well as in normal, inflammatory and tumor tissues. Localization was performed by using the monoclonal antibody (MAb) 5F4 directed against HAF. It was found that 30% of freshly isolated human monocytes expressed the 5F4 antigen. The number of postitive cells increased to 75–90% on day 4 to 7 upon culture and then decreased. Twenty percent of freshly isolated human lymphocytes also stained positively, whereras graunlocytes and platelets were negative. In cryostat sections of normal human tissue (skin, lung, liver, spleen, placenta) 5F4 is positive with capillary endothelial cells and few macrophages. In inflammatory tissue derived from gingivitis and rheumatoid arthrritis, more macrophages than in normal tissues and less endothelial cell were postitive, In tumor tissues some endothelia cells and a subset of tumor‐infiltrating macrophages expressed the antigen. Tumor cells were positive in advanced melanoms, but only occasionlally in stomach carcinomas. We conclude that the angiogenic factor is produced mainly by a subset of inflammatory macrophages which appear to be the principal source of HAF in regenerating or growing tissues.
Isolation of a normal B cell subset with a Burkitt‐like phenotype and transformation in vitro with Epstein‐Barr virus
Authors: Gregory C. D. , Edwads C. F. , Milner A. , Wiels J. , Lipinski M. , Rowe M. , Tursz T. , Rickinson A. B.
Published: February 2007

Epstein‐Barr virus (EBV) is causally linked with endemic Burkitt's lymphoma (BL), a tumour whose homogeneous cell surface phenotype suggests derivation from a particular subset of activated germinal centre B cells in vivo. Endemic BL also shows an unusual form of EBV in fection with downregulation of certain of the virus latent proteins which are constitutively expressed when EBV infects and transforms normal resting B cells in vitro. Here we question whether this virus:cell interaction is unique to malignant BL cells or whether it might be reproduced by in vitro infection of those particular germinal centre cells displaying the BL‐like phenotype. Firstly, we show by biochemical meanns that a subset of normal tonsillar B cells does indeed express the globotriaosylceramide glycolipid BLA and the common acute lymphoblastic leukaemia antigen CALLA, 2 important markers of the BL phenotype. Secondly, using 2‐colour immunofluorescence labelling with anti‐BLA and anti‐CALLA monoclonal antibodies (MAbs), 4 subsets of low buoyant density tonsillar B cells (BLA+ CALLA+, BLA+ CALLA−, BLA− CALLA+, BLA− CALLA−) have been separated by means of a FACS and tested for their susceptibility to EBV‐induced growth transfromation in a limiting dilution assay. The BLA+ CALLA+ (i. e., BL‐like) subset contained the highest proportion of cells already actively in cycle in vivo and gave the lowest yield of transformants, perhaps reflecting the greater efficiency with which EBV transforms resting target cells. Of the cell lines established from the BLA+ CALLA+ population, a significant number retained BLA expression but CALLA was always lost. In 2 further respects, these lines resembled conventional in vitro transformants rather than lines of BL type; thus the cells expressed cellular “activation” antigens (CD23, CD39, CD30, Ki‐24) characteristic of the lymphoblastoid phenotype and contained the full spectrum of EBV latent proteins.
Recombinant IL‐2‐activated NK cells mediate LAK activity against ovarian cancer
Authors: Lotzová Eva , Savary Cherylyn A. , Freedman Ralph S. , Edwards Creighton L. , Wharton J. Taylor
Published: February 2007

We investigated the ability of endogenous and recombinant interleukin‐2 (IL‐2)‐stimulated NK cells from normal donors and ovarian cancer patients to mediate lysis of ovarian tumors, and found that peripheral blood (PB) mononuclear cells of normal donors or cancer patients did not display tumoricidal activity against ovarian cell line or fresh ovarian tumors. In addition, ovarian cancer patients displayed a defect in NK‐cell activity against the highly NK‐sensitive target, K‐562. However, lytic activity against ovarian tumors (including cultured and primary tumors) was induced and that against K‐562 was potentiated in PB of normal donors and PB and peritoneal cavity of ovarian cancer patients after enrichment of LGL on Percoll density gradient or after stimulation of effector cells with recombinant IL‐2 in vitro. The IL‐2‐generated cytotoxic cells in PB were characterized as NK cells displaying CD16+, NKHI (Leu‐19)+, CD3− and CD5− phenotype, while those in the peritoneal cavity were predominantly CD16−, NKHI+, CD3− and CD5−. Studies on the mechanism of IL‐2‐dependent generation of cytotoxicity showed that such an effect was mediated via recruitment of tumor‐binding cells as well as by an increase in the frequency of cytotoxic cells.
Proliferative and/or cytotoxic activity of lymphocyte clones to autologous human melanoma
Authors: Fossati Giuseppe , Anichini Andrea , Squarcina Paola , Mazzocchi Arabella , Parmiani Giorgio
Published: February 2007

Peripheral blood lymphocytes (PBL) of a patient with metastatic melanoma were cultured with autologous melanoma cells (Auto‐Me) and recombinant interleukin 2 (IL‐2) (MLTC‐PBL). Thirty‐five days later, when no cytotoxicity against Auto‐Me or K562 was detectable, MLTC‐PBL were cloned in the presence of Auto‐Me, IL‐2 (25 U/ml) and Daudi cells as feeder. Eighty‐one growing clones were simultaneously screened for proliferative and cytotoxic activity to Auto‐Me. Twenty‐two clones proliferated in the presence of Auto‐Me only, 29 in the presence of IL‐2 only and 41 in the presence of Auto‐Me. Six clones expressed both cytotoxic and proliferative activity to Auto‐Me. The phenotype of 6 proliferative clones tested was CD3+, CD4+, WT31+, CD8−, CD16−, Leu19−, whereas that of 2 cytotoxic‐proliferative clones tested was CD3+, CD8+, Leu19+, WT31+, CD4−, CD16−. Specificity analysis of proliferative response of 6 clones and of cytotoxicity of 7 clones, tested on a panel of 14 different target cells, revealed a complex pattern of reactivity, each clone expressing a peculiar specificity. Our results suggest the possibility of isolating, from melanoma patients' PBL, T‐cell clones with proliferative activity to Auto‐Me and Auto‐Me plus IL‐2, and T‐cell clones which apparently express both proliferative and cytotoxic activity to Auto‐Me.
Subsequent development of acute non‐lymphocytic leukemia in patients treated for Hodgkin's disease
Authors: van der Velden J. W. , van Putten W. L. J. , Guinee V. F. , Pfeiffer R. , van Leeuwen F. E. , van der Linden E. A. M. , Vardomskaya I. , Lane W. , Durand M. , Lagarde C. , Hagemeister F. B. , Hagenbeek A. , Eghbali H.
Published: February 2007

A nested case control study was carried out to investigate the association between treatment of patients with Hodgkin's disease (HD) and the risk of developing acute non‐lymphocytic leukemia (ANLL). Seven Cancer Centers of the International Cancer Patient Data Exchange System of the UlCC participated. A study cohort was selected consisting of 1,681 nonpretreated patients with HD, diagnosed from 1972 through 1978, and followed up through 1984. The median follow‐up time was 66 months. Eighteen cases of leukemia were observed in the cohort. The risk of development of ANLL was significantly greater for male than for female patients. The treatment characteristics associated with an increased risk of developing ANLL were extensive radiotherapy, splenectomy and the chemotherapy combination of vincristine, procarbazine and mechlorethamine.