bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer incidence among medical diagnostic X‐ray workers in China, 1950 to 1985
Authors: Wang Ji‐Xian , Inskip Peter D. , Boic John D. , Li Ben‐Xiao , Zhang Jing‐Yuan , Fraumeni Joseph F.
Published: February 2007

A second follow‐up of 27,011 diagnostic X‐ray workers in China revealed a 21% greater incidence of cancer than expected based on the experience of 25,782 physicians who did not routinely use X‐rays (RR = 1.21; 95% CI: 1.08 to 1.35). This risk is lower than the 50% excess reported previously and reflects, in part, the reduced risk among workers first employed after 1965, when hospital exposures to radiation probably were lower than in earlier years. The X‐ray workers were employed between 1950 and 1985 and followed for an average of 16.1 years. Significantly elevated risks were seen for leukemia (RR = 2.4, n = 34 cases), and cancers of the esophagus (RR = 5.2, n = 19), liver (RR = 1.8, n = 65), and skin (RR = 2.8, n = 9). Cancers of the breast (RR = 1.5, n = 20), thyroid (RR = 1.7, n = 8), and bone (RR = 7.6, n = 4) also occurred more often than expected. Non‐significant deficits were observed for cancers of the oral cavity and pharynx (RR = 0.6, n = 16), colon and rectum (RR = 0.8, n = 20), stomach (RR = 0.8, n = 36), and lung (RR = 0.9, n = 45). Excess risks for leukemia and esophageal cancer were seen among men but not among women. The RR for leukemia was higher for X‐ray workers who began employment before 1970 than for those who started more recently and also for those who were young when employment began. The patterns of risk associated with duration of work, and with age and calendar time of initial employment, suggest that the excesses of leukemia and skin cancer, and, possibly, cancers of the breast and thyroid, were due to occupational exposure to X‐rays. However, there was little evidence that radiation contributed to the increased occurrences of liver or esophageal cancers.
Localization of fluorescent photofrin ii and aluminum phthalocyanine tetrasulfonate in transplanted human malignant tumor LOX and normal tissues of nude mice using highly light‐sensitive video intensification microscopy
Authors: Peng Q. , Nesland Jahn M. , Moan J. , Evensen Jan F. , Kongshaug M. , Rimington C.
Published: February 2007

A comparative kinetic observation of the in vivo biolocalization of Photofrin II (P‐II) and aluminum phthalocyanine tetrasulfonate (AIPCS4) in a transplanted human malignant tumor LOX and in normal tissues of nude mice has been made by means of highly light‐sensitive video intensification microscopy at various intervals after i.p. administration. In the human tumor LOX, transplanted to athymic nude mice, fluorescence of P‐II was observed on the membrane and in the cytoplasm of tumor cells, and in the stroma 4–48 hr post‐injection. From 72 hr post‐injection almost all fluorescing P‐II had disappeared from the membrane of the tumor cells while strong fluorescence was still found in the stroma. AIPCS4 fluorescence was seen mainly in tumorous stroma with none detected in the tumor cells. Almost no fluorescence was found in the tumorous stroma 24 hr after injection. In most normal tissues observed, P‐II was eliminated at a much slower rate than AIPCS4, but the in vivo biolocalization of the 2 drugs was similar. They were observed primarily where collagenous proteins are normally found, i.e. basal lamina, collagenous connective tissue, and in keratinized epithelium, renal epithelium, mononuclear phagocyte system and on the membrane of muscular cells. In addition, AIPCS4 had a strong affinity for the bronchiogenic epithelium. In the skin, P‐II was distributed in keratinized epithelium, hair, hair follicles and their accessory, collagenous connective tissue of dermis, whereas AIPCS4 was present only in hair and collagenous connective tissue of dermis. No fluorescence of P‐II or of AIPCS4 was found in the skin epidermis, nor in the transitional epithelium of the bladder mucosa.
Vitamin A supplements, fried foods, fat and urothelial cancer. A case‐referent study in Stockholm in 1985–87
Authors: Steineck Gunnar , Hagman Ulla , Gerhardsson Maria , Norell Staffan E.
Published: February 2007

In a population‐based case‐referent study of urothelial cancer in Stockholm during 1985‐87, information was obtained from 78% of 418 identified cases and 77% of 511 selected referents. The relative risk (with 95% confidence interval) for intake of vitamin A supplements was 0.5 (0.2–1.0), with a dose‐response relationship with increasing frequency of consumption. Increased risks of urothelial cancer were seen for several fried foods, for example fried meat [relative risk 1.4 (1.0–1.8) for weekly intake] and fried potatoes [relative risk 1.6(1.1–2.6) for weekly intake]. Subjects with a high intake of fried foods, as defined by a collapsed variable, had a relative risk of 2.4 (1.4–4.2). A dose‐response relationship was also seen with an increasing average daily intake of fat [relative risk 1.7 (1.0–2.8) in the highest quintile], but adjusting for fried foods decreased the relative risk, and it is uncertain whether the adjustment allowed for residual confounding. No association was noted for meat other than fried, but the analysis was based on small numbers.
Immunological response of nasopharyngeal carcinoma patients to the Epstein‐Barr‐virus‐coded thymidine kinase expressed in Escherichia coli
Authors: Littler Edward , Newman William , Arrand John R.
Published: February 2007

A bacterial expression system which produces large amounts of the Epstein‐Barr‐virus‐coded thymidine kinase has been developed and used to produce protein for Western blot analysis of a number of human antisera. Interestingly, only sera from nasopharyngeal carcinoma (NPC) patients had any detectable IgA antibody which reacted with the EBV TK. These findings provided the basis for ELISA tests using a crude lysate of the E. coli cells expressing the EBV TK as target antigen. Sera from NPC patients showed high levels of IgA reactive antibodies in this test while other sera did not.
Antibodies against the large subunit of the EBV‐encoded ribonucleotide reductase in patients with nasopharyngeal carcinoma
Authors: Ginsburg Michelle
Published: February 2007

The open reading frame corresponding to BORF2 and encoding the large subunit of the Epstein‐Barr virus (EBV) ribonucleotide reductase has been inserted into the prokaryotic expression vector pUCI9. A 90‐kDa protein was produced when the intact plasmid was used as a template for in vitro DNA‐directed protein synthesis. Using templates generated by restriction digests within the BORF2 open reading frame, in the same system, truncated polypeptides resulted confirming the identity of the 90‐kDa protein. The protein was then produced in a heterologous expression system and used in protein immunoblotting to screen for antibodies in sera from nasopharyngeal carcinoma (NPC), Burkitt's lymphoma (BL) or control subjects. Twenty out of 33 NPC sera were positive for antibodies against the large subunit, 13 of these were positive for both IgG and IgA, whilst 7 were positive for IgG only. Out of 15 BL sera and 10 control sera, none were positive. These results are similar to those observed for other EBV‐encoded enzymes, including the DNase which has been used as an early marker for the development of NPC. The results presented here indicate that antibodies against the large subunit of ribonucleotide reductase could serve as an additional marker for NPC.
Serum and salivary IgA antibodies against a defined epitope of the Epstein‐Barr virus nuclear antigen (EBNA) are elevated in nasopharyngeal carcinoma
Authors: Foong Y. T. , Cheng H. M. , Sam C. K. , Dillner J. , Hinderer W. , Prasad U.
Published: February 2007

The Epstein‐Barr virus nuclear antigen I (EBNA I) is the only latent EBV antigen consistently expressed in malignant tissues of the nasopharynx. A 20‐amino‐acid synthetic peptide, p107 contains a major epitope of EBNA I. We tested sera from 210 patients with nasopharyngeal carcinoma (NPC) and from 128 normal individuals (NHS) for IgA antibodies to p107 using an enzyme‐linked immunosorbent assay (ELISA). Whereas 191/210 (91%) of NPC patients had IgA antibodies to p107, only 17/128 (13.3%) of NHS had such antibodies and only 6/57 (10.5%) of sera from patients with malignancies other than NPC had IgA‐p107 reactivity. Thirty‐nine salivary samples from 46 NPC patients (84.8%) also contained IgA‐p107 antibodies whereas only 3/42 (7.1%) of normal saliva samples were IgA‐p107 positive. The results suggest that IgA antibodies to EBNA I may become a useful, easily measurable, marker for NPC.
Characterization of a 90‐100 kDa tumor‐associated antigen in the sera of melanoma patients
Authors: Euhus David M. , Gupta Rishab K. , Morton Donald L.
Published: February 2007

Using allogeneic antibody, we previously described a highmolecular‐weight glycoprotein in the urine of 68% of melanoma patients. This glycoprotein has been termed urinarytumor‐associated antigen (U‐TAA). A murine monoclonal antibody (MAb) specific for U‐TAA (AD1‐40F4) has been developed. By the use of AD1‐40F4, U‐TAA was detected in serum samples from 63% (33/52) of stage II and stage III melanoma patients, but from only 5% (1/20) of normal controls. This report describes the physical and immunochemical properties of U‐TAA in the serum. The antigen elutes from a DEAE‐Sephacel column in association with IgG in the void volume and as free antigen in a second peak. The molecular mass of the free antigen is 590–620 kDa and it sediments in the region of 28–29% sucrose by density gradient ultracentrifugation. Free antigen has an isoelectric point of 6.1. This high molecular weight antigen is composed of smaller subunits linked by reducible bonds. The AD1‐40F4 reactive epitope resides on a 90–100 kDa subunit. These results provide evidence that U‐TAA which is produced by melanoma cells in vitro is present in the circulation of melanoma patients.
Correlation between collagenolytic activity and grade of histological differentiation in colorectal tumors
Authors: Van Stappen Jos W. J. Der , Hendriks Thijs , Wobbes Theo
Published: February 2007

Collagenolytic activity, extracted from 55 tumor and healthy corresponding intestinal control samples, was determined by 3 different assays using soluble type I and fibrillar type I and III collagen, respectively, as substrate. The enzyme extracted from tumor‐digested collagen type I reconstituted fibrils and yielded the three‐quarter segments characteristic for the action of one of the matrix metalloproteinases: MMP‐I or mammalian collagenase. Metal‐chelating agents such as EDTA and O‐phenanthrolin indeed inhibited this activity. Collagenolytic activities were calculated on the basis of wet weight, total DNA and total extracted protein. Correlations were sought between levels of activity and both clinicopathological stage (Dukes' staging) and grade of histological differentiation. In all the assays applied, significant correlations were found between grade of histological differentiation and collagenolytic activity expressed as the tumor/control ratios: poorly‐differentiated tumors exhibited a higher tumor/control ratio than well‐differentiated tumors. Also, tumors penetrating into the serosa showed a higher tumor/control ratio than tumors invading the muscularis propria only. A relation between collagenolytic activity and clinico‐pathological stage was observed only if activities were calculated on a DNA basis. These results confirm a relationship between the histological appearance of a tumor and its enzymatic potential to degrade interstitial collagens.
Role of IL‐2, IL‐4 and IL‐6 in the growth and differentiation of tumor‐specific CD4+ T helper and CD8+ T cytotoxic cells
Authors: Selvan Rathinam S. , Nagarkatti Prakash S. , Nagarkatti Mitzi
Published: February 2007

We have earlier observed that 1,3‐bis (2‐chloroethyl)‐l‐nitrosourea (BCNU), a chemotherapeutic drug, cured 90–100% of mice bearing a syngeneic la− T‐cell lymphoma (LSA) and furthermore, 100% of the BCNU‐cured mice could reject homologous tumor rechallenge. In the present study, purified CD4+ and CD8+ T cells isolated from BCNU‐cured mice were used to investigate the mechanism by which such T cells recognized and responded to the tumor‐specific antigens. The responsiveness of CD4+ T cells to LSA was dependent on processing and presentation of tumor‐specific antigens by syngeneic la+ splenic antigen‐presenting cells (APC). Such activated CD4+ T cells endogenously produced IL‐2 but not IL‐4 and only IL‐2 acted as an autocrine growth factor inasmuch as anti‐IL‐2 receptor antibodies but not anti‐IL‐4 antibodies inhibited the CD4+ T cell proliferation. In contrast, the CD8+ T cells failed to produce endogenous growth factors when stimulated with LSA alone or with LSA plus APC, and therefore failed to proliferate. However, in the presence of exogenous recombinant IL‐2 (rIL‐2), CD8+ T cells could proliferate directly in response to LSA‐stimulation, even in the absence of APC. Addition of exogenous rIL‐4 alone to cultures induced CD4+ but not CD8+ T cells to proliferate. However, rIL‐4 in the presence of rIL‐2, could synergize and induce tumor‐specific proliferation of CD8+ cells. These data suggested that for IL‐4 to act as a T‐cell growth factor, the presence of IL‐2 was essential, either in the form of endogenously secreted IL‐2 (CD4+ T cells) or exogenous IL‐2 (for CD8+ T cells). In contrast to rIL‐2 and rIL‐4, rIL‐6 failed to induce growth when used alone or in combination with rIL‐2 or rIL‐4. Furthermore, when tested individually, only rIL‐2 but not rIL‐4 or rIL‐6 could support the cytotoxic differentiation of CD8+ T cells. The present study suggests that the early events in responsiveness to LSA tumor may involve activation of the IL‐2‐producing Th1 subpopulation of CD4+ helper cells which in turn activate IL‐2 dependent CD8+ cytotoxic T cells. IL‐4 if produced subsequently, may act synergistically with IL‐2 to promote the growth of CD4+ and CD8+ T cells.
Selective immortalization of a phenotypically distinct epithelial cell type by microinjection of SV40 DNA into cultured human milk cells
Authors: Bartek Jiri , Bartkova Jirina , Lalani El‐Nasir , Brezina Vitezslav , Taylor‐Papadimitriou Joyce
Published: February 2007

An immortal cell line, MMSV‐1, has been developed which exhibits many features of the common luminal epithelial cell of the human mammary gland. The cell line was developed by microinjection of SV40 DNA into individual cells in selected colonies in cultures of human milk epithelial cells. Immunohistochemical staining shows that the MMSV‐1 cells express keratins 7,8, 18 and 19 homogeneously in organized filaments which lead into well‐developed desmosomes. They do not express vimentin or keratins found in stratified epithelia or keratin 14 found in basal cells in the mammary gland. The PEM mucin, recognized by the antibody HMFG‐1, is also expressed and appears to be processed normally. Fibronectin is detected but shows the punctate pattern typical of cultured normal milk epithelial cells. MMSV‐1 cells show a reduced requirement for added growth factors, including cyclic AMP‐elevating agents, but do not grow in agar or form tumours in nude mice. Since the transfected cells could be selected on the basis of an extended in vitro life span, antibiotic resistance markers were not introduced and the cells remain sensitive to hygromycin and neomycin.
CpG methylation of viral DNA in EBV‐associated tumours
Authors: Allday M. J. , Kundu D. , Finerty S. , Griffin Beverly E.
Published: February 2007

In EBV‐immortalized lymphoblastoid cell lines (LCLs) a small number of “latent” proteins are expressed. These are the EBV nuclear antigens, EBNAs 1–6, and a latent membrane protein, LMP. We have investigated the expression of these proteins in a variety of EBV‐associated tumours and cell lines. Whereas transplant and B‐cell lymphomas from cottontop tamarins appear to express the full range of antigens found in LCLs, we and others have found that in Burkitt's lymphomas (BL) and a nasopharyngeal carcinoma (NPC) isolate, EBNA expression is restricted to EBNA‐1. (In NPC, but not in BL, LMP may also be expressed.) In order to ask what restricts the expression of EBNA 2–6 in NPC and BL cells it seemed reasonable to consider the possibility that the DNA sequences normally regulating expression of these antigens could be chemically modified. In this analysis, a tight inverse correlation between methylation of CpG dinucleotides in the 5′ flanking region of the EBNA‐2 gene and the expression of EBNAs 2–6 has been revealed. In the NPC tumour, CpG methylation within the gene is also observed, as is specific methylation over the EBNA‐1 region I and II binding sites (in oriP). The significance of these observations is considered.
c‐fos transfection of 3LL tumor cells turns on MHC gene expression and consequently reduces their metastatic competence
Authors: Kushtai G. , Feldman M. , Eisenbach L.
Published: February 2007

Transfection with c‐fos genes of cells of a highly metastatic (H‐2K−H‐2D+) clone, D 122, of the 3LL carcinoma, causes activation of H‐2K gene expression. Experiments were carried out to test whether these transfectants exhibit reduced metastatic competence. Studying 11 mouse c‐fos, 6 mouse c‐fos and 2 v‐fos transfected clones, we observed that clones expressing high steady‐state levels of the fos mRNA also expressed elevated levels of H‐2K and H‐2D mRNA, and high levels of cell‐surface H‐2K and H‐2D glycoproteins. The transfectants were tested for generation of spontaneous metastasis following intra‐footpad inoculation of the tumor cells. Clones expressing high levels of fos and of H‐2 antigens, particularly those expressing high levels of cell‐surface H‐2Kb molecules, showed a reduction of their metastatic competence. Statistical analysis revealed that c‐fos transfectants are significantly less metastatic than the parental cells. The molecular mechanisms of c‐fos activation of H‐2 genes is briefly discussed.
Proliferative response of T cells from tumor‐immune chickens to carcinogen‐induced fibrosarcoma cells
Authors: Quere Pascale , Tsiagbe Vincent K. , Thorbecke G. Jeanette
Published: February 2007

Immunity to carcinogen‐induced transplantable fibrosarcomas (CHCT‐NYU‐4, ‐97, ‐36 and ‐20) in SC chickens was studied by the ability of spleen cells from NYU‐4 or ‐97 immune chickens to proliferate in response to tumor cells in vitro. Spleen, but not peripheral blood cells, from NYU‐4 immune chickens proliferated significantly more vigorously to gamma‐irradiated NYU‐4 cells than did cells from normal chickens. The proliferative response was not much affected by addition of indomethacin. Spleen cells from NYU‐4‐immune agammaglobulinemic (Aγ) chickens exhibit the same ability to proliferate in presence of gamma‐irradiated NYU‐4 tumor cells. Analysis of the phenotype of the T‐cell component involved in proliferation showed that the proliferative response was significantly decreased by removal of CT4+ cells through indirect panning. Removal of CT8+ cells enhanced background proliferation without affecting the total thymidine incorporation in the presence of tumor cells. Immune spleen cells usually gave highest responses to the immunizing tumor, but also exhibited cross‐reactivity to cells from other individual tumors induced by the same carcinogen.
In vitro therapeutic targeting of neuroblastomas using 125I‐labelled meta‐iodobenzylguanidine
Authors: Guerreau Dominique , Thedrez Philippe , Fritsch Paul , Saccavini Jean‐Claude , Metivier Henri , Nolibe Daniel , Masse Roland , Coornaert Sabine , Chatal Jean‐François
Published: February 2007

The use of labelled radiopharmaceuticals such as metaiodobenzylguanidine (m‐IBG) enables neuroblastomas and other malignant cells from neural crests to be visualized. In vitro study of cellular incorporation into human neuroblastoma lines (SK‐N‐SH, SK‐N‐MC, LAN I) showed that only the SK‐N‐SH line retained iodine‐125 m‐IBG (125I‐m‐IBG) significantly. Fifty‐five percent of the initial activity was retained after 1 hr incubation at a concentration of 10−7 M of m‐IBG (specific activity: 1,480 MBq/mg). Beyond this value, m‐IBG uptake mechanisms were saturated. Study of release kinetics showed a rapid first phase (50% released after 4 hr) and a slower second phase (30% of the value retained at the equilibrium point was present after 48 hr), indicating the existence of a storage compartment. Autoradiography studies confirmed the intracytoplasmic localization of m‐IBG and showed that a low percentage (3 to 5%) of SK‐N‐SH cells strongly retained m‐IBG. Cytotoxicity tests showed that SK‐N‐SH cell growth was significantly reduced during the first days of culture, following 2 hr incubation with 1,500 KBq of 125I‐m‐IBG, whereas no toxic effect on SK‐N‐MC cells was found at the same activity. Moreover, the toxic effect observed in the SK‐N‐SH line was clearly related to the use of 125I‐m‐IBG since the same activity of 1,500 KBq of noncoupled 125I was without effect. For the latter line, colonyforming capacity was reduced for activities of 150 and 1,500 KBq of 125I‐m‐IBG, with respectively 32% and 38% lower survival rates. The cytotoxic effect of labelled m‐IBG was, however, limited in non‐saturating concentrations because the specific activity used was too low. Moreover, the low number of cells reconcentrating m‐IBG is indicative of the heterogeneous cellular composition of the SK‐N‐SH line.
Effect of gamma interferon on HLA class‐I and ‐II transcription and protein expression in human breast adenocarcinoma cell lines
Authors: Jabrane‐Ferrat Nabila , Faille Annick , Loiseau Pascale , Poirier Odette , Charron Dominique , Calvo Fabien
Published: February 2007

The spontaneous expression of HLA class‐I and class‐II molecules in 5 human breast carcinoma cell lines, MCF‐7, T47D, ZR75‐I, HSL‐53, MDA‐MB 231, and their modulation during IFN‐γ treatment, are reported. The expression of cell‐surface determinants was examined by indirect immunofluorescence using monoclonal antibodies (MAbs) specific for HLA class‐I and class‐II (DR, DQ and DP) antigens. The biosynthesis and maturation of these molecules were analyzed by 2‐dimensional gel electrophoresis analysis (2D‐PAGE) of class I, DRα, β and invariant immunoprecipitates. Transcription was analyzed by Northern blot hybridization with HLA class‐I and ‐II cDNA‐specific probes. In all cell lines, more than 80% of cells expressed HLA class‐I antigens at their surface. 2D‐PAGE and mRNA studies showed a variable basal level of HLA class‐I biosynthesis and transcription with a constant increase after 1,000 U/ml IFN‐γ treatment. HLA class‐II determinants were totally absent from the surface of MCF‐7, MDA MB231, ZR75‐I and T47D but they were detected in a small subpopulation of HSL‐53 cells (DR 6%, DQ 6%, DP 20%). Spontaneous biosynthesis of HLA‐DR molecules in immunoprecipitates analyzed by 2D‐PAGE or transcripts in Northern blot were not detected in the 5 cell lines. Treatment with 1000 U/ml IFN‐γ Induced or increased the expression of HLA class‐II molecules in all cell lines but DQ expression was variable. While T47D, ZR75‐I and HSL‐53 increased their transcripts and antigen expression, MDA, MB231 and MCF‐7 showed no DQ mRNA transcript. Biochemical analysis of the DR products revealed a classical α, β and invariant (Ii) chain pattern, but indicated a constant glycosylation defect in the invariant chain in all cell lines, associated with weak expression of the β chain and the presence of an extra spot of low molecular weight in the acidic part of the gel. Thus, post‐transcriptional events did not appear to be totally controlled by IFN‐γ in the different cell lines. These differences in DQ expression and glycosylation process in different breast cancer cells may be important in the activation of the immune response among different individuals.
The sialosyl Lewisa ganglioside is present in tumorigenic human urothelial cell lines
Authors: Ugorski Maciej , Påhlsson Peter , Dus Danuta , Nilsson Bo , Skouv Jan , Radzikowski Czeslaw
Published: February 2007

The sialosyl Lewisa antigen was identified in a ganglioside extract from a malignant human urothelial cell line (Hu 1703He) by fast atom bombardment mass spectrometry. The presence of this antigen in urothelial cell lines with varying tumorigenic properties was further studied using the 19‐9 monoclonal antibody (MAb). The sialosyl Lewisa ganglioside was expressed only in the tumorigenic cell lines. Thus, the expression of this antigen is a marker of malignancy for human urothelial cell lines. Mass spectrometry also suggests that the fucosyl GM1 ganglioside was expressed in the Hu 1703He cell line. This was confirmed using the F12 MAb, specific for fucosyl GM1. However, the expression of this antigen was not confined to cell lines with tumorigenic properties.
Melanoma risk by age and socio‐economic status
Authors: Kerkpatrick Constance S. , Lee John A. H. , White Emily
Published: February 2007

To explore the relationship between melanoma incidence, socio‐economic status (SES), and site of occurrence, 1,804 cases of melanoma in Washington State from 1974‐85 were analyzed by mean income of census tract of residence. (Census tracts are geographic divisions of state counties for which demographic information is provided by state agencies.) For males aged 30‐69, as expected, the risk increased with in come. Unexpectedly, at age 70 and over the trend was reversed (the heterogeneity of the age relationship was unlikely to be due to chance). In the older men, the increase with low income was found in the cases reported as Hutchinson's melanotic freckle and those which were not, being statistically significant in the latter. These findings suggest a role for long continued sun exposure in the etiology of malignant melanoma.
Aromatic amine acetyltransferase as a marker for colorectal cancer: Environmental and demographic associations
Authors: Wohlleb James C. , Hunter Carolyn F. , Blass Baxter , Kadlubar Fred F. , Chu David Z. J. , Lang Nicholas P.
Published: February 2007

In this pilot, case‐controlled investigation of 43 colorectal and 41 control male patients, we compared associations of colorectal cancer with the aromatic amine acetyltransferase polymorphism, nutritional and demographic characteristics, medical histories, industrial and occupational histories, and exposures from home environments and personal habits. Persons with the “fast” acetylator trait were at greater risk of colorectal cancer (odds ratio: 2.48; 95% confidence interval: 1.02, 6.03). Results that differed from previous reports were positive associations of colorectal cancer with agricultural and manufacturing industries and with consumption of meats prepared by smoking, curing, and barbecueing. As expected, exercise frequency, cruciferous vegetables, and dietary fiber served as protective factors.
The tumour spectrum in hereditary non‐polyposis colorectal cancer: A study of 24 kindreds in the netherlands
Authors: Vasen Hans F. A. , Johan G. , Offerhaus A. , Den Hartog Jager Frieda C. A. , Menko Fred H. , Nagengast Fokko M. , Griffioen Gerrit , Van Hogezand Ruud B. , Heintz A. Peter M.
Published: February 2007

The hereditary colonic cancer syndrome without polyposis, hereditary non‐polyposis colorectal cancer (HNPCC), is usually divided into 2 main categories: hereditary site‐specific colorectal cancer (Lynch syndrome I) and colorectal cancer in association with other forms of cancer (Lynch syndrome II). One problem associated with Lynch II is the uncertainty as to which types of cancer form part of the hereditary tumour spectrum. The present study was performed to obtain more information about the tumour spectrum of HNPCC. In the 24 HNPCC families studied, 104 patients had colorectal cancer (mean age at diagnosis: 46 years) and in 4 of the families this was the only type of cancer to occur. Sixty‐five extra‐colonic tumours were diagnosed in 20 families. Endometrial carcinoma was found in 16 patients belonging to 12 families. Cancer of the stomach occurred in 10 patients representing 5 families, and mainly in the older generations. Urinary‐tract tumours were found in 8 patients from 4 families. Second primary tumours were diagnosed in 13 of the 16 patients with endometrial cancer, in 4 of the 10 patients with stomach cancer and in 7 of the 8 patients with a urinary‐tract tumour. Many other types of carcinoma were found as well, but less frequently. In our families, the trait appears to be transmitted by patients with cancer of the stomach, endometrium or urinary tract, because some of their children have developed colorectal cancer. The findings suggest that, in these 24 HNPCC families, carcinomas of the endometrium, stomach and urinary tract belong to the hereditary tumour spectrum. Definite assignment of tumours to this spectrum will become possible only after a sensitive and specific biomarker becomes available. The screening programme should depend on which and how many extra‐colonic tumours occur in a family.
Generation and characterization of monoclonal antibodies to prostate secretory protein
Authors: Wright George L. , Huang Chia‐Ling , Lipford Grayson , Beckett Mary Lou , Liang Hong Mei , Haley Cara , Newhall Kathy , Morningstar Michelle
Published: February 2007

Monoclonal antibodies (MAbs) were produced against a highly purified preparation of prostate secretory protein (PSP) isolated from normal seminal plasma. Fifteen antibodies were selected for further evaluation based on their strong reactivity and specificity for PSP. All the MAbs had a specificity for prostate epithelial cells and none reacted to any of a variety of normal tissues as determined by immunoperoxidase staining. Six of the MAbs were selected for further immunohistochemical evaluation based on their ability to recognize different antigenic determinants. Using competitive binding immunoassays, a variety of overlapping specificities were observed with at least 2 distinct epitopes identified. Although some staining variability was noted, the 6 antibodies, in general, gave the same pattern of tissue reactivity. Both the normal prostate and the benign prostate hyperplastic ductal epithelial cells stained intensely, with 78 to 100% and 50‐100% of the cells staining, respectively. The number and often the staining intensity of the tumor cells decreased as the tumor became more undifferentiated. Approximately 40 to 100% and 15 to 70% of the tumor cells stained in the moderately‐differentiated and well‐differentiated carcinoma tissues, respectively, whereas either no staining was observed or less than 20% of the tumor cells stained in the poorlydifferentiated and undifferentiated tumors. Most of the metastatic prostate tumors showed either no staining or scattered stalning in a few cells (i. e., less than 20%).
Identification of a 43‐kda nuclear antigen associated with proliferation by monoclonal antibody k 112
Authors: Quak Jasper J. , Dongen Guus Van , Koken Marie A. E. , Brakkee Joost G. P. , Scheper Rik J. , Balm Alfons J. M. , Jong Luitzen De , Snow Gordon B. , Meijer Chris J. L. M.
Published: February 2007

Monoclonal antibody (MAb) K 112 was generated after a single intrasplenic immunization with a recurrent laryngeal squamous‐cell carcinoma. The antibody detects a 43‐kDa nuclear antigen, with a pl of 5.4, which is expressed only in cycling cells. Expression is typically seen in a granular pattern excluding the nucleoli. During mitosis the bulk of the antigen is diffusely distributed in the cytoplasm. Identical reactivity was observed for tissues or cells of all mammalian species tested. These data indicate that MAb K 112 recognizes a protein belonging to the class of cell‐cycle‐related nuclear antigen molecules.
Genotype markers and proto‐oncogene analysis in the cd30‐positive “malignant histiocytosis” del cell line with t(5;6)(q35;p21)
Authors: Gogusev J. , Barbey S. , Nezelof C.
Published: February 2007

The DEL cell line isolated from a patient who died of malignant histiocytosis exhibits a reciprocal chromosomal translocation t(5;6) (5q35;6p21). The cells were analyzed for lg(Jh), TCR β‐gene rearrangements and proto‐oncogene expression pattern, using a panel of molecularly cloned probes that in cluded c‐fms, c‐myc, c‐myb, c‐pim, c‐fos, N‐myc, c‐sis, c‐fgr as well as the virally derived probes v‐ki‐ras and v‐src. Consistent levels of expression of c‐fms, c‐myc, c‐myb, c‐ki‐ras and c‐fgr were identified in cells from several in vitro passages as well as from the heterotransplanted tumors in nude mice. Transcripts homologous to the c‐fos, c‐src and c‐sis were not observed. Southern blot study of DNA showed that the banding pattern of the screened proto‐oncogenes was not altered. Furthermore, Southern blot analysis demonstrated monoallelic immunoglobulin heavy chain (IgJh) rearrangement but a normal germ‐line configuration of the K light chain and TCR β‐genes. These results appear to imply that a T‐ or B‐cell origin can be eliminated and that several activated protooncogenes, usually expressed in immature MPS cells (c‐fms) and myeloblastic cells (c‐fgr), may be implicated in the proliferative activity of the DEL cell line, the stem of which may be a primitive, ancestral myelomonocytic cell.
Human multi‐drug‐resistant cancer cells exhibit a high degree of selectivity for stereoisomers of verapamil and quinidine
Authors: Eliason James F. , Ramuz Henri , Kaufmann Franz
Published: February 2007

An in vitro cell proliferation assay was developed to measure the capacity of substances to overcome multi‐drug resistance (MDR). The assay is a modification of the MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) method. The inclusion of cell titration curves for each concentration of the resistance modifier (RM) allows the IC50 of the RM to be calculated and provides empirical correction of the cell survival curves for the effect of the RM when it is combined with a standard cytotoxic drug, vincristine. The resistance modification index (RMI) is defined as the ratio of the IC50 of vincristine obtained in control cultures divided by that measured in the presence of RM and is linearly related to the dose of RM. The RMI0.1, the RMI at a one‐tenth the IC50 of the RM, provides a relative comparison between the activities of different RMs at non‐toxic doses. The results obtained using the MDR cell line, KB‐8‐5, show that I‐(‐)‐verapamil is approximately 4 times more active than d‐(+)‐verapamil in modifying MDR. The racemic mixture has an intermediate activity. A similar comparison between the epimers quinidine and quinine shows that, at equimolar doses, quinine has a higher RMI but, because it is more toxic, the RMI0.1 is about one‐half of that of quinidine. These results demonstrate the importance of comparing the resistance‐modifying activities of different compounds at doses relative to their own toxicity.
Newly established human retinoblastoma cell lines exhibit an “immortalized” but not an invasive phenotype in vitro
Authors: Griegel Sahine , Hong Chen , Frötschl Roland , Hülser Dieter F. , Greger Valerie , Horsthemke Bemhard , Rajewsky Manfred F.
Published: February 2007

Retinoblastoma (RB), an intraocular childhood tumor occurring in a hereditary (mostly bilateral) or non‐hereditary (unilateral) form, is associated with the inactivation of both alleles of a putative tumor suppressor gene (RB‐I) located on chromosome 13q14. Both the process of RB development and the biological characteristics of RB cells are as yet poorly understood. We have established 7 new RBL lines (RBL13, RBL14, RBL18 and RBL30, derived from unilateral RB; and RBL7, RBL15 and RBL20, derived from bilateral RB). Southern blot analyses of restriction fragment length polymorphisms in DNA samples from 6 cell lines revealed loss of constitutional heterozygosity at one or several polymorphic locion chromosome 13 in 4 cases. Gross deletions involving the RB‐1 locus and amplification of the N‐myc gene were not detected in any of the RBL lines. The phenotypic properties of the RBL lines were analyzed in comparison with cells from the original RB tumors, with 4 RB lines established by others (RB383, RB355, RB247C3 and Y79) and with the adenovirus‐EIA‐transformed human retinoblast line HER‐Xhol ‐CC2. It was found that RB tumors consist of phenotypically heterogeneous cell subpopulations with varying nutrient requirements and differentiation potential in vitro. All cell lines showed the typical characteristics of established (immortalized) cells. In some cases, cells from original RB tumors or cell lines were able to form colonies when cell aggregates of 2‐10 cells were suspended in semi‐solid agar medium; however, anchorage‐independent colonies never developed from single cells. Cell lines RBL13, RBL18, RB247C3, RB355, RB383 and Y79 were tested for invasion into embryonic chick heart fragments in vitro and found to be non‐invasive. None of the RBL or RB lines were tumorigenic in nu/nu (T‐) mice. Y79 cells (propagated in culture for many years) exhibited properties distinctly different from those of the other cell lines, and thus cannot be considered phenotypically representative of RB cells.
A study of human small‐cell lung carcinoma (hsclc) cell lines with different sensitivities to detect relevant mechanisms of cisplatin (cddp) resistance
Authors: Hospers G. A. P. , Meuer C. , De Leij L. , Uges D. R. A. , Mulder N. H. , De Vries E. G. E.
Published: February 2007

The cisplatin(CDDP)‐resistant cell line GLC4‐CDDP shows a variety of differences from the parent line GLC4. The aim of this study was to determine which of the observed changes correlated with the degree of resistance and was therefore relevant to the phenomenon of CDDP resistance. For these experiments we used cells of the sensitive hSCLC cell line GLC4 and the in vitro‐acquired CDDP‐resistant sublines GLC4‐CDDP3 and GLC4‐CDDP11, with a resistance factor (RF) of 3 and 11 respectively for CDDP and of 1.8 and 7.4 respectively for carboplatin. Carboplatin was used, in addition to CDDP in seeking relevant mechanisms. No consistency was found between the RF and the growth pattern or antigen expression, cellular volume, doubling time, cellular or nuclear platinum (Pt) content or the level of Pt‐non‐histone chromatin protein (NHCP) binding. A correlation was found between the RF and the level of glutathione (GSH), and a trend was found for the level of Pt‐DNA binding, Pt‐GG adduct content and the amount of interstrand cross‐links (ISC). These changes might therefore be relevant for the development of resistance. These findings are compatible with a GSH‐induced reduction of the amount of reactive Pt in the resistant cell, resulting in a lower net platination and toxic Pt‐DNA adduct formation.
Serum changes the response of cultured morris hepatoma 7777 cells to autocrine growth factors
Authors: Guzik Krzysztof , Klein Andrzej
Published: February 2007

The addition of calf serum to culture medium alters the biological response of Morris hepatoma 7777 (MH) cells to autocrine growth factors isolated from conditioned medium of the investigated cells. Acetic acid (AA) extract obtained from conditioned medium of MH cells showed a change in anchorage‐independent growth‐regulatory activity from stimulation (serum‐free) to inhibition (10% calf serum). Two protein fractions of apparent molecular weight 15 and 7.5 kDa isolated from AA‐extract by Bio‐Gel P‐60 filtration also changed their growth‐regulatory activity after supplementation of culture medium with calf serum. The contradictory effect of autocrine regulators estimated in soft agar using the 3H‐thymidine (3H‐TdR) incorporation test and colony formation assay gave generally comparable results, except in the case of the 15‐kDa fraction. The most active 7.5‐kDa fraction stimulated 3H‐TdR incorporation and colony formation in serum‐free medium up to about 300 and 500% respectively, while in the presence of 10% calf serum inhibition of about 20 and 50% has been observed. Our results suggest that the fraction contains an autocrine growth factor(s), whose activity is inverted in the presence of serum.
Natural history of colorectal polyps and the effect of polypectomy on occurrence of subsequent cancer
Authors: Murakami Ryosuke , Tsukuma Hideaki , Kanamori Shinobu , Imanishi Kiyoshi , Otani Toru , Nakanishi Katsumi , Fujimoto Isaburo , Oshima Akira
Published: February 2007

To elucidate the natural history of colorectal polyps and to observe the influence of endoscopic polypectomy on the incidence of colorectal cancer, we conducted a retrospective cohort study of all patients who had undergone colonoscopic examination at the Center for Adult Diseases, Osaka, between April 1974 and December 1985. The study subjects consisted of a control group (760 non‐polyp patients) and a polyp group (648 polyp patients, including 136 treated by polypectomy at the initial examination). These subjects were followed up until the end of 1987 by record linkage with the Osaka Cancer Registry's file to observe the occurrence of colorectal cancer. The O/E (observed/expected numbers derived from the general population) was 5.1 (95% confidence interval = 2.5‐9.4) and 1.0 (0.1‐3.6) for the polyp and control group, respectively. When subjects in the polyp group were categorized into polypectomy and non‐polypectomy sub‐groups, the O/E was 2.3 (0.1‐12.6) and 8.0 (3.4‐15.8) respectively. The relative risk of undergoing polypectomy to developing subsequent cancer was estimated at 0.3 (0.1‐2.1). These results suggest an increased risk of developing cancer among polyp patients and the possibility of prophylactic effect of polypectomy against subsequent cancer. A large‐scale and longterm follow‐up study is required to confirm these findings.
Early indicators of efficacy of breast cancer screening programmes. Results of the florence district programme
Authors: Paci Eugenio , Ciatto Stefano , Buiatti Eva , Cecchini Silvia , Palli Domenico , Turco Marco Rosselli Del
Published: February 2007

A mammographic breast cancer screening programme has been ongoing in the Florence District (Italy) since 1970 and a favourable impact of screening on breast cancer mortality of women aged 50‐70 has been shown by means of a casecontrol study. Two hundred and eleven screen‐ and 116 interval‐detected cancers in the period 1975‐1986 have been identified, and detection rates calculated, for first and repeated screening test (2nd to 7th). Overall, 22,980 subjects were screened and 44,988 repeated tests performed. The observed number of interval cancers has been compared with the expected incident cancers and their ratio (O/E) studied at different time intervals since last test. The O/E ratio at the third year since the last test was 0.98 for the age‐group 40–49 0.50 (95% CI: 0.23‐0.95) and 0.39 (95% CI: 0.26‐0.94) for the 50‐59 and 60‐69 groups, respectively. The prevalence/incidence ratio (P/I) was then calculated as an early indicator of efficacy. For the 40‐49 age‐group the P/I ratio at first test was 1.09, suggesting poor anticipation of diagnosis. In contrast, for women 50‐59 and 60‐69 results suggest quite a good diagnosis anticipation (P/I: 3.14; 4.82), confirming the result of the previous case‐control study on mortality reduction. The proportion of advanced carcinomas (stage II or worse) and 5‐year survival have been analysed and discussed. The study confirms the opportunity of using early indicators of screening efficacy for monitoring of screening services.
Immune status as a determinant of human papillomavirus detection and its association with anal epithelial abnormalities
Authors: Melbye Mads , Palefsky Joel , Gonzales John , Ryder Lars P. , Nielsen Henrik , Bergman Olav , Pindborg Jens , Biggar Robert J.
Published: February 2007

One hundred and twenty Danish homosexual men were enrolled to characterize risk factors for anal type‐specific human papillomavirus (HPV) expression and to examine its association with anal epithelial atypia. Detection of HPV strongly correlated with immunosuppression measured by Tlymphocyte subset markers and rose nearly linearly from 7.3% among subjects with CD4/CD8 ratios above 1.0 to 35.3% among those with a ratio below 0.4 (p trend = 0.003). No association was found between presence of HPV and a wide range of lifestyle factors including number of sex partners/year, smoking, alcohol consumption and illegal drug intake. However, self‐reported history of anal condyloma in the past year was correlated with HPV (p < 0.001). Simultaneous testing for presence of HPV in the oral cavity showed evidence of HPV 16, 18 and 31, 33, 35. Anal smears were abnormal in 19.5% of the men and correlated strongly with presence of HPV (OR = 601, p < 0.0001). Type‐specific associations were found with HPV 31/33/35 (OR = 8.5) and HPV 16/18 (OR = 3.1) only. The association remained significant after adjusting for immune status. Overall, HPV was detected in 50% of the cases with abnormal smears. However, HPV was found in all subjects with abnormal smears and a CD4/CD8 ratio below 0.4, compared to only 3 of 14 subjects with abnormal smears and a ratio ± 1.3. In conclusion, (I) HPV may be missed in a substantial number of infected subjects with a normal immune system. This may have an impact on studies trying to describe risk factors for HPV transmission and its correlation with cancer development. (2) The finding of HPV 16,18 and 31,33,35 in the oral cavity makes oral‐genital sexual activity at least a hypothetical route of transmission for these HPV types. (3) HPV appears to play a central role in the development of anal epithelial abnormality.
A model‐based analysis of the hip project for breast cancer screening
Authors: Van Oortmarssen G. J. , Habbema J. D. F. , Lubbe J. T. H. N. , Van Der Maas P. J.
Published: February 2007

A computer simulation approach is used to test assumptions about sensitivity of mammography and physical examination, and about the duration of preclinical screendetectable breast cancer. Values between 50% and 80% for the combined sensitivity of the 2 tests give a good explanation of the results of the HIP randomized trial of breast cancer screening. The mean duration of the preclinical stage can vary from 1.6 years for high sensitivity values to 2.7 years for low values. In comparison with previous analyses of the HIP data, our estimate for the sensitivity is lower, and the mean duration of the preclinical stage is longer. This is a consequence of the use of a more detailed model in our analysis, allowing for a more complete use of the HIP data in testing model assumptions. Similar analyses of data from recent screening projects in The Netherlands resulted in compatible estimates for the duration of preclinical breast cancer.
Cancer incidence in migrants to new south wales
Authors: McCredie Margaret , Coates Marylon S. , Ford Joyce M.
Published: February 2007

Cancer incidence in migrants to New South Wales (NSW) from the British Isles, north‐central, eastern and southern Europe, the Middle East and Asia has been compared with that in Australian‐born residents using data from the NSW Central Cancer Registry for 1972‐84. Indirectly standardized incidence ratios (SIRS) were low in migrants from all 6 regions for melanoma of skin and cancers of lip and, except in men from eastern Europe, colon. Oesophageal, rectal and prostatic cancers also tended to be relatively less common. Cancers which were more common than in the Australian‐born were those of the stomach and, for men, bladder (except in the Asian‐born). Migrants from different regions showed variations from the cancer pattern of the Australian‐born population which, for the most part, were predictable from the known incidence of cancer in the countries within the region of origin. Exceptions were the high relative incidence of nasopharyngeal cancer in migrants from southern Europe and bladder cancer in men from all regions other than Asia.