bluuebunny/crossref_metadata_2025 huggingface dataset:
Multifactorial analysis of parameters influencing chemosensitivity of human cancer xenografts in nude mice
Authors: Fujita Fumiko , Fujita Masahide , Taguchi Tetsuo , Shimozuma Kojiro , Sakamoto Yasuo , Kimoto Yasuhiko , Hirai Toshihiro
Published: February 2007

The results of single‐agent chemotherapy, with 11 anti‐cancer agents, of 15 human gastro‐intestinal and breast cancer lines xenografted into nude mice indicate inherent individuality of chemosensitivity spectrum of each tumor. The following 9 parameters have been measured as factors possibly relevant to chemosensitivity of tumor tissue or tumor‐bearing mice: grade of histological differentiation, vascularity, percentage of necrosis, VDT, 3H‐thymidine LI, human LDH activity in the cancer tissue, tissue/serum LDH ratio, TdR Pase activity, and serum CEA. These parameters exhibited presumably constant values for each tumor line. Chemosensitivity, i.e., inhibition of tumor growth by a given drug, was used as the dependent variable, and values of the 9 parameters in each cancer as the explanatory variables. Multiple regression analyses with stepwise deletion were performed for each of the 11 drugs. The equations for 8 drugs exhibited coefficients of determination of over 70%, and in particular those for M‐83 (a derivative of mitomycin C), nimustine hydrochloride and doxorubicin exceeded 80% by equations with 3–4 parameters. Consequently, the estimated value for each line of effectiveness derived from the equations for these 8 drugs showed remarkable coincidences with the actual values for the inhibition rates of the corresponding drugs.
Acquisition of tumorigenic potential in the human myoepithelial HBL100 cell line is associated with decreased expression of HLA class I, class II and integrin β3 and increased expression of c‐myc
Authors: Krief P. , Saint‐Ruf C. , Bracke M. , Boucheix C. , Billard C. , Billard M. , Cassingena R. , Jasmin C. , Mareel M. , Azzarone B.
Published: February 2007

The human breast cell line HBL100 acquires the capacity to invade normal tissues and to replace them by proliferation in vitro only at high passage levels (HPL). These cells therefore are a useful model for studying tumor progression in vitro. We have analyzed the expression of cell‐surface markers supposed to be involved in the control of the neoplastic process. Quantitative flow cytometry has revealed that: (I) spontaneous expression of HLA class‐1 antigens strongly decreases in HPL HBL100 cells vs. LPL cells, which parallels amplification and over‐expression of c‐myc oncogene; (2) HLA DR antigens can be induced by IFN‐gamma in LPL but not in HPL HBL100 cells; (3) HBL100 cells secrete a soluble protein factor which specifically inhibits HLA DR induction by IFN‐gamma even in heterologous cell systems; (4) 50% of LPL HBL100 cells express integrin β3, whereas HPL HBL100 cells lose this antigen; (5) this cell line is myoepithelial in origin, since 100% of HBL100 cells exhibit the CD 10 antigen. Our data stress a role of HLA antigens, of some integrins and of c‐myc in the acquisition of malignant potential by myoepithelial mammary cells of the HBL100 line.
Properties of a non‐tumorigenic human cervical keratinocyte cell line
Authors: Stanley Margaret A. , Browne Helena M. , Appleby Mark , Minson Anthony C.
Published: February 2007

A human cervical keratinocyte cell line, W12, has been initiated from a low‐grade cervical lesion histologically diagnosed as CIN I. This cell line has, to date, undergone over 300 generations in vitro with an average doubling time of 30 hr: an aneuploid karyotype has developed with progressive in vitro growth. W12 contains HPV16 DNA present at approximately 100 copies and the state of the viral DNA over a number of passages has been examined. The HPV13 DNA is stably maintained at high copy number over several passages and restriction enzyme analysis together with electrophoresis of uncleaved viral DNA indicate that it is present predominantly as the episomal molecule. W12 cells exhibit a typical keratinocyte morphology and, when transplanted into the flank of the nude mouse, form an epithelial lesion with the histological features of CIN I/II.
Androgen receptors, androgen‐dependent proliferation, and 5α‐reductase activity of small‐cell lung cancer cell lines
Authors: Maasberg M. , Rotsch M. , Jaques G. , Enderle‐Schmidt U. , Weehle R. , Havemann K.
Published: February 2007

We investigated the influence of testosterone on binding to established small‐cell lung cancer (SCLC) cell lines and were able to show specific high‐affinity and low‐capacity binding sites in some cell lines with a typical receptor size, using sucrose density gradient centrifugation. In addition, we demonstrated marked growth stimulation with testosterone and dehydrotestosterone using different androgen‐receptor‐positive small‐cell lung cancer cell lines. This growth stimulation could be counteracted by the addition of anti‐androgens like cyproterone acetate or flutamide. The presence of 5α‐reductase activity, 17ß‐hydroxysteroid‐dehydrogenase and 3α‐hydroxy‐steroid‐dehydrogenase activities could be demonstrated, suggesting testosterone metabolism of small‐cell lung cancer cell lines.
Adriamycin action on human breast cancer cells: Enhancement by medroxyprogesterone acetate
Authors: Shaikh Naeem A. , Owen Alison M. , Ghilchik Margaret W. , Braunsberg Hannelore
Published: February 2007

Exposure of cultured human breast cancer cells (MCF‐7) to medroxyprogesterone acetate (MPA) prior to treatment with adriamycin (ADR) enhanced the effect of the cytotoxic drug on cell yield after further growth of viable cells. Pre‐treatment with oestradiol (E2) produced similar synergism, but no such effect was observed using dexamethasone. Exposure to ADR before MPA led to an additive effect, but not to synergism. When cells resistant to the growth‐inhibitory action of MPA were examined, progestogen/drug synergism could still be demonstrated. We conclude that the effects of ADR, like those of methotrexate and vincristine, can be enhanced by pre‐treatment with MPA and that further clinical trials of such a regimen are needed.
Possible involvement of chromosome 1 in in vitro immortalization: Evidence from progression of a human adenoma‐derived cell line in vitro
Authors: Paraskeva Christos , Harvey Amanda , Finerty Susan , Powell Susan
Published: February 2007

We have previously reported that continuous in vitro passage in the presence of 3T3 feeders of a non‐tumorigenic adenoma‐derived epithelial cell line, designated PC/AA, resulted in its becoming immortal. At early passage PC/AA was normal diploid, whereas every cell of PC/AA late passage had an isochromosome I(q) which led us to suggest that abnormalities of chromosome I may be involved in tumour progression. We now report the isolation of a 3T3‐feeder‐independent variant of early‐passage PC/AA, designated PC/AA/FI, which was immortal in vitro and remained non‐tumorigenic. Each cell of PC/AA/FI again has an isochromosome I(q), like the late‐passage PC/AA. However, with PC/AA/FI it is the other chromosome I of the homologous pair which is involved in the formation of the isochromosome I(q). This is possible to determine because of the polymorphic cen‐tromeric heterochromatin on chromosome I of the early‐passage PC/AA. With the late‐passage PC/AA (grown with 3T3 feeders) the homologue with the large C‐band has given rise to an isochromosome I(q) whereas with PC/AA/FI it is the other homologue with the smaller C‐band which has given rise to this isochromosome. Both the immortal PC/ AA/FI and the immortal PC/AA late passage, therefore, have independent abnormalities involving chromosome I. These results indicate that chromosome I may be involved in in vitro immortalization.
Expression of 7F7‐antigen, a human adhesion molecule identical to intercellular adhesion molecule‐1 (ICAM‐1) in human carcinomas and their stromal fibroblasts
Authors: Vogetseder Werner , Feichtinger Hans , Schulz Thomas F. , Schwaeble Wilhelm , Tabaczewski Piotr , Mitterer Manfred , Böuck Günther , Marth Christian , Dapunt Otto , Mikuz Gregor , Dierich Manfred P.
Published: February 2007

The 7F7‐antigen is a widespread 85‐kDa membrane adherence molecule involved in heterotypic adhesion between PHA‐blasts and fibroblasts. Immunofluorescence analysis of COS cells transfected with clone p1CAM‐1 indicated that 7F7‐antigen is identical with ICAM‐1, the ligand for the contact molecule LFA‐1. We have investigated the expression of ICAM‐1 on several human carcinomas. Tumor cells in most carcinomas, with the exception of squamous‐cell carcinomas, expressed very little ICAM‐1 or none at all. In contrast, marked expression of this molecule was observed on fibrous tissue in the vicinity of carcinoma cells, its intensity correlating with lymphatic infiltration in these tumors. We also examined the expression of ICAM‐1 on carcinoma cell lines and its induction by treatment with interferon‐gamma (IFN‐γ). The inducibility of ICAM‐1 expression on cultured fibroblasts by several lymphokines suggests that the expression of ICAM‐1 in the vicinity of carcinoma cells is effected by lymphokines produced by activated lymphocytes/macrophages within the tumor.
The role of alcohol in oesophageal cancer in non‐smokers, and of tobacco in non‐drinkers
Authors: La Vecchia Carlo , Negri Eva
Published: February 2007

Data from a hospital‐based case‐control study of oesophageal cancer conducted in Northern Italy were used to analyse the risk associated with alcohol in non‐smokers and with tobacco in non‐drinkers. Out of a total of 250 cases (198 males, 52 females) and 1,089 controls (800 males, 289 females), there were 38 cases and 404 controls who described themselves as lifelong non‐smokers. Among these persons, the relative risk was not different for teetotallers and moderate drinkers (<4 drinks per day), but increased markedly for higher levels of alcohol consumption. The point estimates were 2.1 for 4 to 8 and 3.6 for over 8 drinks per day, and the trend in risk was statistically significant. Likewise, among 30 cases and 189 controls who were non‐drinkers, the point estimates were 2.0, 3.9 and 6.2 for smokers of <15, 15–24 and ≥25 cigarettes per day, with, again, a statistically significant trend. This study supplies further evidence that both alcohol and tobacco are strongly related to the risk of oesophageal cancer, even in the absence of exposure to the other risk factor. This confirms previous indications from a study in Calvados, France and also provides statistically significant epidemiological evidence of an independent role of exposure to tobacco alone in the aetiology of oesophageal cancer. The relative risks associated with exposure to either of the 2 factors among subjects not exposed to the other were readily comparable to the estimates adjusted for the other factor in the overall data‐set, thus further confirming the independent effect of alcohol and tobacco on oesophageal carcinogenesis.
Identification of a human epithelial cell surface protein sharing an epitope with the C3d/epstein‐barr virus receptor molecule of B lymphocytes
Authors: Young L. S. , Dawson C. W. , Brown K. W. , Rickinson A. B.
Published: February 2007

This work examines the basis for our earlier observation that certain monoclonal antibodies (MAbs) specific for the B‐cell‐associated C3d/Epstein‐Barr virus (EBV) receptor molecule CD21 also react with the surface of some epithelial cells. Of 9 proven anti‐CD21 MAbs now examined on frozen sections of human nasopharynx, tonsil and ecto‐cervix, only 3 (HB5, anti‐B2, AB1) showed staining of stratified epithelium; 2 of these (HB5, anti‐B2) also reacted with the surface of epithelial cells freshly dispersed from these sites. The proportion of HB5‐ and anti‐B2‐reactive cells in primary epithelial cultures fell to a low but stable level within days of explantation, while almost all permanently established epithelial cell lines, whether SV40 virus‐transformed or of malignant origin, were not reactive with either MAb. This contrasts with the pattern of expression of another surface marker also found selectively on cells of the lymphoid and epithelioid lineages, the CDw40 antigen. Staining with CDw40 MAbs on epithelial sections was usually restricted to the basal (proliferating) layer, but the proportion of CDw40‐positive cells increased to a relatively high level in normal epithelial cultures; furthermore, most epithelial cell lines expressed this antigen. Immunoprecipitation from the surface of metabolically labelled epithelial cells with the anti‐CD21 MAb HB5 yielded a protein of approximate MW 200 kDa, clearly different in size from the 145 kDa CD21 molecule on B cells. This 200 kDa protein was identified on fresh ecto‐cervical epithelium, on primary cultures of a laryngeal carcinoma and on one unusual SV40‐transformed epithelial cell line. We conclude that stratified human epithelial cells express a 200 kDa surface molecule which is antigenically related to, but not identical with, the CD21 antigen on B cells. It remains to be seen whether this epithelial cell protein can function as an EBV receptor.
Multiple infections in cases of cervical cancer from a high‐incidence area in tropical Africa
Authors: Schmauz R. , Okong P. , De Villiers E.‐M. , Dennin R. , Brade L. , Lwanga S. K. , Owor R.
Published: February 2007

The presence of several infections was determined in tissue and serum samples from 34 cases and 23 controls seen in 1984–85 at Mulago Hospital in Kampala, Uganda. When assessing single infections, association with cervical cancer could be shown for 5 agents, namely by Southern blot assay for human papillomavirus types 16 and 18 (HPV), and by serological tests at varying levels of antibody titres, for herpes simplex virus type 1 and/or 2 (HSV), cytomegalovirus (CMV), Epstein‐Barr virus, viral capsid antigen (EBV‐VCA), and Chlamydia trachomatis (CLT). Due to interaction, HSV and CMV were associated with cervical cancer only when infection by both of these agents was demonstrable. In the assessment of the simultaneous presence of these 5 infections, moderately high antibody titres were taken as the cut‐off point for infection by HSV, CMV, EBV‐VCA, and CLT. This showed that 3 and 4 infections at a time were seen in the majority of the cases in contrast to the controls with essentially no more than 2 such infections. A linear trend in the rise of risk for cervical cancer was noted with increasing number of infections.
Mammary adenocarcinomas induced by medroxyprogesterone acetate: Hormone dependence and egf receptors of BALB/c In vivo sublines
Authors: Lanari Claudia , Kordon Edith , Molinolo Alfredo , Pasqualini Christiane Dosne , Charreau Eduardo H.
Published: February 2007

Mammary adenocarcinomas were induced by medroxyprogesterone acetate (MPA) in female BALB/c mice. From 5 primary tumors, 9 different sublines were established by s.c. transplantation into syngeneic female mice; these developed after a long latent period (4‐12 months). Each subline was transplanted both into 4 mice treated with 40mg of MPA depot (s.c. contralaterally to the tumor inoculum) and into 4 non‐treated mice. Of the 9 sublines, 6 proved to be hormonedependent (MPA‐D) and 3 hormone‐independent or autonomous (MPA‐I). However, even the autonomous lines, when treated with MPA, showed a slight increase in growth. All MPA‐D lines had a high content of ER (20‐254 fmoles/mg of protein), PR (63‐710), PRL‐R (44‐74) and low or nondetectable EGF‐R. Of the 3 MPA‐I sublines that were studied, 2 showed a high content of ER (16‐125), PR (27‐708), PRL‐R (19‐70) and EGF‐R (29‐65) while the other one had a low content of ER (0‐36), PR (0‐13), no EGF‐R and moderate PRL‐R (15‐52). Spontaneous mammary tumors of BALB/c and C3H origin, which also showed an MPA‐l pattern of tumor growth, had high levels of EGF‐R. We postulate that MPA has a direct effect on mammary tumor cells in MPA‐D lines and that the expression of EGF‐R is correlated with an autonomous pattern of growth.
Monoclonal anti‐idiotypic antibody mimicking a tumor‐associated sialoglycoprotein antigen induces humoral immune response against human small‐cell lung carcinoma
Authors: Barth Andreas , Waibel Robert , Stahel Rolf A.
Published: February 2007

We have previously described the tumor‐associated sialoglycoprotein antigen sGP90‐135 defined by the murine LAM8 MAb. The antigen is characterized by strong membrane expression in a proportion of small‐cell carcinomas of the lung, but little or no expression on normal tissues of epithelial or neural origin or on blood cells. With the aim of obtaining anti‐idiotypic antibodies which might be useful as surrogates for sGP90‐135 in vaccination studies, LOU rats were immunized with LAM8 MAb and their spleen cells fused with Y3 rat myeloma cells. The LY8‐229 hybrid was selected by an antiidiotype competition radioimmunoassay on antigen‐positive target cells. LY8‐229 was shown to be a rat IgG1 with high specificity for LAM8 combining site. Solubilized small‐cell carcinoma extract, as well as antibody SEN16, which recognizes the same tumor‐associated antigen sGP90‐135, selectively inhibited 125I‐LY8‐229 binding to LAM8. Serum from BALB/c mice and DA rats immunized with anti‐idiotypic antibody LY8‐229 showed reactivity with antigen‐positive target cell lines, but not with antigen‐negative control cell lines. The induction of a specific immune response in 2 different species by the anti‐idiotypic antibody LY8‐229 suggests that LY8‐229 bears the internal image of the antigen sGP90‐135 and that it might be a candidate for immunotherapy trials in cancer patients.
Anti‐tumor effect of recombinant murine TNF‐alpha (rmutnfa) given by continuous I.V. infusion as compared to repeated I.V. injections in a rat liver metastasis model
Authors: Scheringa M. , Keizer A. , Jeekel J. , Marquet R. L.
Published: February 2007

Anti‐tumor effects of TNF in animal models are well documented. Therapeutic use of TNF, however, is hampered by its toxicity. In rats a single intravenous (i.v.) injection of 40 μg/kg is lethal. When given by continuous i.v. infusion, much higher doses are well tolerated. To compare the therapeutic efficacy of rMuTNF given either as repeated i.v. injections or as a continuous infusion, we have used a liver metastasis model (tumor CC531). The number of liver metastases at day 28 after tumor inoculation served as a parameter. The route of administration, administration schedule and dose, did, in general, not influence the effect produced by rMuTNFa. Only early continuous infusion had an effect on the number of liver metastases. A sublethal dose, given as a late continuous infusion, had no significant effect. It thus appears that rTNFa, even when administered at high doses, is not a very efficient anti‐tumor agent. Attention should rather be focused on the use of rTNFa in combination with other substances, for example, interferons.
Characterization of immunoglobulin mrna expression in burkitt lymphoma cell lines
Authors: Anker Roberto , Caldwell James , Brokaw Jane , Pollok Brian A.
Published: February 2007

Immunoglobulin heavy‐ and light‐chain mRNA of II Burkitt lymphoma (BL) cell lines (9 African and 2 American) were analyzed for various structural characteristics. In agreement with previous results at the protein level, all the BL cell lines express heavy‐chain mRNA transcripts of the μ class. Surprisingly, a high μ/μm mRNA ratio was found in 2 lgM‐producing BL cell lines (Raji and CCL85), that do not secrete immunoglobulin. Variable region gene use was also assessed in the cell lines: while 4 out of 7 endemic BL cell lines use VH genes that belong to the VH3 gene family, no clear bias in the expression of particular VH or VL gene families among this sampling of BL lines was found. Northern blot analysis of immunoglobulin transcripts in endemic BL cell lines did show that 2 such lines (AG876 and HTB62) expressed truncated heavy‐chain transcripts; RNA sequence analysis of the VH region demonstrated different abnormal 5‐localized RNA splicing events for the 2 shortened μ transcripts. The light‐chain mRNA in these 2 cell lines also showed structural abnormalities and, in the case of HTB62, 3 different K light‐chain transcripts are produced (of elongated, native and truncated sizes). In vitro translation of mRNA from HTB62 showed μ and K chain proteins corresponding with the relative size for each message.
Variations in serum alkaline dnase activity in rats during growth and treatment of tumors sensitive or resistant to therapy
Authors: Economidou‐Karaoglou Anna , Brasseur Francis , Lans Marc , Taper Henryk S. , Roberfroid Marcel B.
Published: February 2007

Serum alkaline DNase activity (SADA) was investigated in rats receiving s.c. transplants of tumor cells sensitive or resistant to chemotherapy. Serum samples from each animal were collected before transplantation, during the development of tumors and after therapy. Within a few days after transplantation of both tumor lines (sensitive or resistant), SADA levels decreased progressively to 52% of the normal pre‐transplantation level (p < 0.01). This decrease in SADA preceded by 4 to 5 days the appearance of any palpable tumor mass. In all untreated animals as well as in treated rats bearing resistant tumors, SADA remained at a low level until death. In rats bearing tumors sensitive to therapy a progressive increase in SADA was observed after treatment, paralleling tumor regression. When tumor regression was complete, SADA resumed the levels of activity measured prior to transplantation.
The prevalence of antibody to p42 of HTLV‐1 among ATLL patients in comparison with healthy carriers in Japan
Authors: Yokota Tsutomu , Cho Min‐Ji , Tachibana Nobuyoshi , McLane Mary Fran , Takatsuki Kiyoshi , Lee Tun‐Hou , Mueller Nancy , Essex Max
Published: February 2007

A gene product (p42) of the long open reading frame, now termed tax, of the viral genome of human T‐cell leukemia virus type 1 (HTLV‐1) may be related to the transformation of T cells in adult T‐cell leukemia‐lymphoma (ATLL). To evaluate its association with the disease, we compared the prevalence of antibody to p42 in sera obtained from 105 HTLV‐1 carriers and 64 ATLL patients from southwest Japan. The prevalence of the anti‐p42 antibody reactivity was 63% among carriers and 31% among cases. The cases were more than 3 times as likely to lack antibody to p42 than carriers, the relative odds (OR) = 3.4, p = 0.001. When the samples were tested for antibody against p24, the most immunogenic core protein, the prevalence was somewhat higher among carriers (65%) than in cases (52%), but not significantly so (p = 0.15). Among the healthy carriers, the correlation between the prevalence of both antibodies was high (p = 0.001), and only 25% of those who had antibody to p24 lacked antibody to p42. However, among the cases, reactivity to both antigens was independent (p = 0.52), and 65% of those with antibody to p24 lacked antibody to p42, OR = 6.3, p = 0.0004. Thus the strongest serologic marker of ATLL following diagnosis was lack of reactivity to p42, particularly among those subjects with anti‐p24. Whether this altered response is present prior to disease remains to be determined.
Cancer among 1,348 offspring of survivors of childhood cancer
Authors: Hawkins M. M. , Draper G. J. , Smith R. A.
Published: February 2007

The occurrence of cancer among the 1,348 offspring of 2,441 survivors of childhood cancer, treated before 1978, was investigated. Information was obtained through a questionnaire sent to the general practitioners of these survivors. Twenty‐three of 52 offspring born to survivors of heritable retinoblastoma developed retinoblastoma; the heritable form of retinoblastoma is known to be transmitted to offspring as an autosomal dominant. None of the 94 offspring born to the 54 survivors of unilateral retinoblastoma with no family history of the disease have developed the disease. This implies that it is unlikely that more than 9% of survivors of unilateral retinoblastoma with no family history have the germ‐cell mutation; consequently it is unlikely that more than 4% of their offspring will be affected. Among the 1,199 offspring born to 629 survivors of other childhood malignant disease, who produced children, one acute monocytic leukaemia and one acute lymphoblastic leukaemia were observed. This is more than expected on the basis of the general population (one‐tailed p = 0.04). However, the types of cancer observed in these 2 offspring and their parents conform to a previously described familial aggregation of cancers. Only a small number of children were born to survivors who received therapy that was potentially germ‐cell mutagenic, and thus it is not possible to make any accurate estimation of their risk of malignant disease.
Cancer among New York men at risk of acquired immunodeficiency syndrome
Authors: Biggar Robert J. , Burnett William , Mikl Jaromir , Nasca Philip
Published: February 2007

In the United States, New York City has had the greatest number of subjects at risk of AIDS for the longest period of time. This population therefore serves as an indicator of changes in cancer risk which may emerge among persons at risk from AIDS. Using a proportional incidence method, we surveyed cancers occurring among single (a surrogate for homosexual) young men and married young men in Manhattan, the rest of New York City, and the remainder of New York State. The baseline period was established earlier to be 1973–76, during which time no cases of Kaposi's sarcoma were observed among single men in Manhattan. By 1985, the frequency of Kaposi's sarcoma in this group was increased 1,850‐fold (compared with expected cases derived from other registries). In the same group, the increase of non‐Hodgkin's lymphoma was 6.2‐fold (p for trend <0.0001), with excesses of Burkitt's lymphoma and immunoblastic lymphoma being most noticeable. Diagnoses of Hodgkin's disease increased markedly in 1985 but not earlier. Since this pattern did not follow that of the AIDS epidemic in this area, we suggest that Hodgkin's disease is not an AIDS‐associated tumor. Hepatoma was diagnosed more frequently in single young men during the 1980s but similar increases also were observed in married men and thus may be unrelated to AIDS. Thus, only Kaposi's sarcoma and non‐Hodgkin's lymphoma appear to be AIDS‐associated tumors, at least so far. With better treatment and longer survival, it remains possible that other tumors will emerge as part of the AIDS epidemic.
Colorectal cancer and diet in an asian population—A case‐control study among Singapore Chinese
Authors: Lee H. P. , Gourley L. , Duffy S. W. , Estève J. , Lee J. , Day N. E.
Published: February 2007

A hospital‐based case‐control study of diet and colorectal cancer was conducted among Chinese in Singapore (who constitute 77% of the population). A total of 203 cases and 425 controls were included. A history of the usual dietary intake one year prior to interview was taken using a quantitative food frequency questionnaire. Daily intakes of nutrients and selected food items were computed and stratified by tertiles of the control range, to assess risk in low‐, medium‐ and high‐intake categories. Effects were adjusted in analysis for age, sex, Chinese dialect group and occupation. For cancers of colon and rectum combined, significant observations were a protective effect of high cruciferous vegetable intake (OR = 0.50, p < 0.01) and a predisposing effect of a high meat/vegetable consumption ratio (OR = 1.77, p < 0.05). Similar results were observed for colon cancer alone. For rectal cancer alone (only 71 cases), significant (p < 0.05) protective effects were observed for high intakes of protein (OR = 0.61), fibre (OR = 0.46), beta‐carotene (OR = 0.54), cruciferous vegetables (OR = 0.51) and total vegetables (OR = 0.51). When further assessed by multiple logistic regression, tests for trend and assessment of risk in the extreme highest and lowest quintiles of the control range, the factors consistently significant were cruciferous vegetable intake and the meat/vegetable ratio. A particularly high relative risk was also noted in association with low coffee consumption (OR = 1.59, with p < 0.05 for trend). No consistent trends were noted for fat or fibre intakes. For non‐dietary variables investigated, a history of cholecystectomy increased the risk of both cancers combined (OR = 3.43, p < 0.05) and colon cancer alone (OR = 4.39, p < 0.01). This study in an Asian population of countries of Southern and Eastern Asia newly undergoing industrialization and in which rapid economic change is reflected in changing cancer patterns, suggests that the protective effects of certain dietary constituents, notably the cruciferous vegetables, may be more important than the hitherto stressed carcinogenic potential of fat and protein.
Molecular characteristics and physical state of human papilloma virus DNA change with progressing malignancy: Studies in a patient with epidermodysplasia verruciformis
Authors: Yabe Yoshiro , Tanimura Yoshie , Sakai Akiko , Hitsumoto Takako , Nohara Nozomi
Published: February 2007

In order to establish the role of human papillomavirus (HPV) in carcinogenesis of epidermodysplasia verruciformis (EV), the presence, the molecular characteristics and the physical state of HPV DNA in a benign lesion, a primary carcinoma and a metastatic carcinoma developing in the same EV patient were studied and compared. Of the 2 HPV DNAs isolated from benign macular lesions, only one (a subtype of HPV 5) was detected in both primary and metastatic tumors. Only one normal species of viral DNA molecule was detected in the benign lesion, whereas most, if not all, viral DNA molecules present in the carcinoma (both primary and metastatic) were aberrant ones. The major viral DNA molecule in the primary carcinoma was a large HPV DNA with duplicated 40% subgenomic segments, and was present as free episomes. The major viral DNA molecule in the metastatic carcinoma was the 40% subgenomic segment itself, lacking the remaining 60% segment of the viral genome, and was integrated within cellular DNA. Thus, HPV DNA was present in tumors at any stage of malignancy, and its molecular characteristics and physical state changed not only with the development but also with the enhancement of malignancy, consistently conserving its defined 40% subgenomic segment as the predominant viral sequences. Our results suggest that HPV 5 may be actually involved in carcinogenesis in EV patients.
The EcoRI rflp of c‐MOS in patients with non‐Hodgkin's lymphoma and acute lymphoblastic leukemia, compared to geriatric and non‐Geriatric controls
Authors: Chenevix‐Trench G. , Southall M. , Kidson C.
Published: February 2007

We have used Southern blot analysis to type individuals for the presence or absence of a rare EcoRI RFLP at the c‐mos proto‐oncogene locus. This polymorphism has previously been reported to be associated with cancer. Ninety‐eight patients with non‐Hodgkin's lymphoma (NHL) or acute lymphoblastic leukemia (ALL) and 154 cancer‐free individuals, including 108 geriatric patients with no family history of cancer, were studied. Because 4 geriatric patients (aged 67‐94) were found to have the rare c‐mos allele (A2), and the frequency of this A2 allele was no higher among the lymphoma/leukemia patients than among cancer‐free individuals, it is unlikely that it constitutes a marker for NHL or ALL.
Human papillomavirus infection and anal cancer
Authors: Beckmann Anna Marie , Daling Janet R. , Sherman Karen J. , Maden Christopher , Miller Beth A. , Coates Ralph J. , Kiviat Nancy B. , Myerson David , Weiss Noel S. , Hislop T. Gregory , Beagrie Marjorie , McDougall James K.
Published: February 2007

To study the association of human papillomavirus (HPV) infection with anal cancer, we examined tissue specimens from 126 patients with malignant lesions of the anal skin or mucosa. The patients were enrolled in a population‐based, case‐control study of ano‐rectal cancer which is being conducted in the state of Washington and the Province of British Columbia. Histologic sections from formalin‐fixed, paraffinembedded tissues were tested for the presence of HPV DNA by in situ hybridization with biotin‐labelled HPV 6, 11, 16, 18 and 31 DNA probes. HPV DNA sequences were found in tumor tissues from 24 of the 126 subjects (19.0%). When only squamous neoplasms are considered, 23 of 70 subjects (32.9%) had lesions which contained detectable HPV DNA. One HPV‐positive patient had a cloacogenic carcinoma that contained regions of squamous differentiation and it was in these squamous cells that HPV DNA was localized. Of the 23 squamous lesions that harbored detectable HPV DNA, 8 contained HPV 6, 10 contained HPV 16, I contained HPV 18 and 4 contained an unclassified virus type(s). HPV DNA was found in tissues from 14 patients with carcinoma‐in situ and 10 subjects with invasive carcinoma. These results demonstrate that some malignant tumors of the anus, in both men and women, are associated with HPV infection. We conclude that the anal squamous epithelium is another site where infection with the common genital tract HPVs may carry a risk of malignant transformation.
A core protein epitope of the polymorphic epithelial mucin detected by the monoclonal antibody SM‐3 is selectively exposed in a range of primary carcinomas
Authors: Girling Anne , Bartkova Jirina , Burchell Joy , Gendler Sandra , Gillett Cheryl , Taylor‐Papadimitriou Joyce
Published: February 2007

The monoclonal antibody (MAb) SM‐3, which was raised to chemically deglycosylated milk mucin, reacts with an epitope present on the core protein of this mucin which we have referred to as PEM (polymorphic epithelial mucin). Although this mucin is abundantly expressed by both the lactating breast and breast carcinomas, the antibody SM‐3 shows very little or no reactivity on the former but does react with 92% of breast carcinomas. Furthermore, SM‐3 stains primary carcinomas of the lung, colon and ovary, but on the corresponding normal tissue the epitope is expressed at a much reduced level or not at all. These results indicate that an epitope masked in the normal mucin is exposed in the mucin produced by tumour cells, perhaps due to aberrant glycosylation. An extensive immunohistochemical study of other normal tissues reveals that the majority show only weak focal staining with SM‐3 or none at all, the distal tubules and collecting ducts of the kidney, and sebaceous glands being the only normal tissues studied to show homogeneously positive staining.
Diet and nasopharyngeal carcinoma: A case‐control study in Guangzhou, China
Authors: Yu Mimi C. , Huang Teng‐Bo , Henderson Brian E.
Published: February 2007

We conducted interviews on 306 histologically confirmed incident cases of nasopharyngeal carcinoma (NPC) occurring in residents of Guangzhou City, China, who were under the age of 50 years, and an equal number of age‐, sex‐, and neighborhood‐matched controls. We also interviewed 110 mothers of patients under age 45 years and 139 mothers of controls who were matched to patients under age 45 years, to obtain information on childhood exposures of study subjects. Exposure to salted fish, whether in adulthood or in childhood, was significantly associated with an increased risk of NPC. The association was strongest for exposure during weaning, and exposures at all other periods were no longer related to NPC risk after adjustment for exposure during weaning. Besides salted fish, childhood exposure to 5 other preserved foods (fermented fish sauce, salted shrimp paste, moldy bean curd, and 2 kinds of preserved plum) was significantly related to NPC, and the effects were independent of salted fish exposure. Finally, cases ingested significantly less fresh vegetables and fruits than controls, especially during early childhood, and the differences were not explained by their differing consumption pattern of salted fish and other preserved foods.
ETN‐1: A new human endometrial carcinoma cell line producing ascites and distant metastases in nude mice
Authors: Kruitwagen R. F. P. M. , Poels L. G. , Willemsen W. N. P. , Croes H. J. E. , Smeets D. F. C. M. , Beck J. L. M. , Hanselaar A. G. J. M. , Ramaekers F. C. S. , Rolland R. , Jap P. H. K.
Published: February 2007

A human carcinoma cell line (ETN‐I) has been established from a skin metastasis of a moderately differentiated adenocarcinoma of endometrial origin. The cell line has been so far maintained for 27 months through 55 passages, growing as a monolayer as well as in 3‐dimensional clusters with a population doubling time of 72 hr. The number of chromosomes per cell varied from 39 to 107 (average number 61.0 ± 19.8), with a modal number of 46–48. Seven clonal marker chromosomes were detected. Flow cytometric analysis revealed a population of pseudo‐tetraploid cells (DNA index 2.1) next to a pseudo‐diploid population (DNA index 1.1). The epithelial character of the cells was confirmed by a positive immunocytochemical reaction using monoclonal antibodies (MAbs) to different keratins, the epithelial cell markers BW 495/36 and HMFG‐2, as well as by the presence of many junctional complexes. The tumour cells retained a positive reaction with the anti‐ovarian carcinoma OV‐TL 3, OV‐TL 10 and OC 125 MAbs, although the reaction was markedly diminished in comparison with the original tumour. Tumour cells inoculated subcutaneously in nude mice produced well differentiated adenomatous tumour nodules with formation of glandular lumina and basal lamina. Tumour cells injected intraperitoneally produced malignant ascites and regional as well as distant metastases of adenomatous character.
Induction of Epstein‐Barr virus in B‐lymphoblastoid cells by human immunodeficiency virus type 1
Authors: Lai Patrick K. , Li Xu , Volsky David J.
Published: February 2007

Individuals infected with the human immunodeficiency virus (HIV), the etiologic agent of acquired immunodeficiency syndrome (AIDS), often show symptoms associated with reactivation of Epstein‐Barr virus (EBV). In this study, we show that exposure of EBV‐positive B lymphocytes to HIV‐1 in vitro induced the EBV replicative cycle in these cells, as evidenced by an increased proportion of cells expressing EBV early antigens (EA) and capsid antigens (VCA). Reactivation of EBV by HIV‐1 appeared to be virus‐dose‐dependent and required virus penetration and expression in B cells. Although HIV‐1 RNA was detected by in situ hybridization in the majority of HIV‐1‐infected B lymphocytes, induction of EA and VCA was transient and limited to less than 20% of the cell population. The tumor‐promoting phorbol ester 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA) and HIV‐1 acted synergistically and had similar kinetics in inducing the expression of EBV. Direct reactivation of EBV by HIV‐1 may contribute to the role of EBV as a factor in the genesis of AIDS‐related conditions.
Cells derived from sporadic and aids‐related Kaposi's sarcoma reveal identical cytochemical and molecular properties in vitro
Authors: Werner Sabine , Hofschneider Peter Hans , Roth Willi Kurt
Published: February 2007

We have established 40 cell cultures from biopsies of 5 patients with sporadic Kaposi's sarcoma (KS) and compared them with cell cultures derived from KS biopsies of AIDS patients. Immunocytochemical staining of sporadic KS cells revealed the same endothelial cell markers as those expressed on AIDS‐KS cells, indicating that both types of KS might be of endothelial cell origin. In contrast to clinical features, in vitro growth properties showed no differences. KS cells of both types reveal a low degree of malignancy but can be distinguished from fibroblasts by a higher passage number in low serum concentrations and a more pronounced dependence on platelet‐derived growth factor (PDGF). The DNA of 12 cell lines of both types of KS was negative for genomic equivalents of hepatitis B virus (HBV), cytomegalovirus (CMV) and, in the case of AIDS‐KS, for human immunodeficiency virus (HIV). No rearrangements or amplifications of several oncogenes, often involved in human tumors, were detected. The expression of these oncogenes by sporadic and AIDS‐KS cells, as analyzed by Northern blotting, was comparable to that of normal dermal fibroblasts from the same patients. Our results indicate that the 2 types of Kaposi's sarcoma possess identical cytochemical and molecular properties. They are probably weakly malignant neoplasms of endothelial cell origin, and paracrine growth stimulation appears to be important for their maintenance and progression.
Microbial flora in the gastrointestinal tract abolishes cytostatic effects of α‐difluoromethylornithine in vivo
Authors: Hessels J. , Kingma A. W. , Ferwerda H. , Keu J. , Van Den Berg G. A. , Muskiet F. A. J.
Published: February 2007

Although treatment with the ornithine decarboxylase inhibitor α‐difluoromethylornithine (DFMO) leads to depletion of intracellular polyamines and to related growth inhibition in vitro, its cytostatic effects in vivo are disappointing. This may be due to abolition of DFMO‐induced growth inhibition by polyamines released during normal body cell turnover, to dietary polyamines, or to putrescine synthesized by the microbial flora in the Gl tract. We studied selectively (aerobic) and totally (aerobic + anaerobic) Gl tract‐decontaminated L1210‐bearing mice fed with 3 types of diet differing in their polyamine and carbohydrate residue contents and treated with combinations of intraperitoneal DFMO and oral deuterium‐labelled putrescine. Our data show that, irrespective of diet type, total decontamination markedly potentiates the moderate tumor growth inhibition that is caused by DFMO alone. During total decontamination, growth‐inhibited L1210 cells accumulate in the G0,/G1, phase of the cell cycle. Although orally administered deuterium‐labelled putrescine gave rise to deuterium labelling of L1210 putrescine, spermidine and spermine, the polyamine levels in our diets played only a minor role.
Diet and colorectal cancer with special reference to fiber intake
Authors: Heilbrun Lance K. , Nomura Abraham , Hankin Jean H. , Stemmermann Grant N.
Published: February 2007

In this nested case‐control study, 8,006 American Japanese men were examined and interviewed with a dietary questionnaire from 1965 to 1968. After a follow‐up period of over 16 years, 102 colon and 60 rectal cancer incident cases were identified. Dietary data from these patients and from 361 cancer‐free controls were analyzed for intake of dietary fiber (DF), vitamins, minerals, macronutrients, and selected food groups. We found a significant (p= 0.042) negative association of DF and colon cancer risk among low fat intake men (<6I g/d). In this subgroup, the men consuming <7.5 g/d of DF had an adjusted relative risk (RR) for colon cancer of 2.28 (95% CI 0.93‐5.60), compared to those consuming ⩾ 14.8 g/d of DF. We also observed (among the complete group of subjects) a significant (p= 0.011) negative association between vitamin C intake and the risk of colon cancer. Men in the lowest quintile of vitamin C intake (<37 mg/d) had an adjusted colon cancer RR of 1.87 (95% CI 1.03‐3.37), compared to men in the highest quintile (⩾ 160 mg/d). We view these dietary associations with colon cancer risk with caution. There were no other significant associations of dietary variables with colon cancer risk. Also, there were no significant associations between intake levels of DF, micronutrients, or food groups and rectal cancer risk.
Risk factors for cervical cancer in greenland and Denmark: A population‐based cross‐sectional study
Authors: Kjaer Susanne K. , Telsen Chantal , Haugaard Birthe J. , Lynge Elsebeth , Christensen René B. , Møller Knud A. , Jensen Henning , Poll Paul , Vestergaard Bent F. , De Villfers Ethel‐Michele , Jensen Ole M.
Published: February 2007

The incidence of cervical cancer in Greenlandic women aged 20‐39 years is nearly 6 times higher than in Danish women of the same age. Possible determinants of cervical cancer incidence were investigated in a population‐based cross‐sectional study. From Nuuk (Greenland) and Nykøbing Falster (Denmark) a sample of 800 women aged 20‐39 years was drawn at random. A total of 586 and 661 women were studied in Greenland and Denmark, respectively. All underwent a personal interview. In Greenland, 13% of the women reported first intercourse before the age of 14 in contrast to 3.5% in Denmark, and nearly 85% of the Greenlanders had their sexual debut before the end of the 16th year of age whereas this applied to only 45% of the Danish women. The prevalence of women with 0‐1 lifetime sexual partner was 20.4% in Denmark, and only 1.7% in Greenland. In contrast, 53.2% of the Greenlandic women reported more than 20 partners and 22.4% more than 40 partners. The corresponding figures for Denmark were 3.6% and 0.3%, respectively. In Greenland the most common contraceptive method was the use of intra‐uterine devices (73.6%), whereas, in Denmark, oral contraceptive use was most frequent (87.9%). Few Greenlanders had ever used “barrier” contraceptives (diaphragm: 1.4%; condom: 18.1%) compared to Denmark (diaphragm: 10.1%; condom: 53.9%). As many as 87.4% were current smokers in Greenland (Denmark: 53.6%) and 5.6% claimed to have never smoked, whereas this applied to 35.3% in Denmark. The indications of a higher sexual activity (multiple partners, early age at first intercourse) in Greenland compared to Denmark are in line with the observed higher rates of sexually transmitted diseases and with the hypothesis that differences in cervical cancer incidence between Greenland and Denmark are determined by aspects of sexual background.
Serum concentration of beta‐carotene and intake frequency of green‐yellow vegetables among healthy inhabitants of Japan
Authors: Shibata Atsuko , Sasaki Ryuichiro , Ito Yoshinori , Hamajima Nobuyuki , Suzuki Sadao , Ohtani Motohiko , Aoki Kunio
Published: February 2007

Serum levels of beta‐carotene were measured among healthy inhabitants (671 males and 948 females) of 2 towns in Japan to determine the association between the levels and intake frequency of green‐yellow vegetables. Those individuals who consumed green‐yellow vegetables frequently showed higher levels of serum beta‐carotene than those who ate them less often. The influences of alcohol drinking, smoking, obesity and age on serum beta‐carotene levels were similarly observed for the 2 areas. The factors listed above were used for adjustment, giving a significant association between intake frequency of green‐yellow vegetables and serum beta‐carotene level. The proportion of the subjects who rarely consumed green‐yellow vegetables was larger among smokers than among non‐smokers. There was a large difference in serum beta‐carotene levels between the 2 towns, which could not be explained by alcohol drinking and smoking. Women showed statistically significantly higher serum beta‐carotene levels than men.
Cancer risks due to occupational exposure to formaldehyde: Results of a multi‐site case‐control study in montreal
Authors: Gérin Michel , Siemiatycki Jack , Nadon Louise , Dewar Ron , Krewski Daniel
Published: February 2007

A case‐control study was undertaken in Montreal to investigate the possible associations between occupational exposures and cancers of the following sites: oesophagus, stomach, colo‐rectum, liver, pancreas, lung, prostate, bladder, kidney, melanoma and lymphoid tissue. In total, 3,726 cancer patients and 533 population controls were interviewed to obtain detailed lifetime job histories and information on potential con‐founders. Each job history was translated into a history of occupational exposures. Because of current concerns about formaldehyde carcinogenicity, we carried out a special analysis of the association between exposure to formaldehyde and each type of cancer covered by this study. Separate statistical analyses were carried out for each type of cancer using population controls as well as a control series drawn from among the other cancer sites in the study. Although nearly a quarter of all subjects had undergone occupational exposure to formaldehyde, the levels of exposure were in general quite low. There was no persuasive evidence of an increased risk of any type of cancer among men exposed to these levels of formaldehyde. However, the possibility of a small increase in risk could not be ruled out.