bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics of n‐4‐hydroxyphenyl‐retinamide and the effect of its oral administration on plasma retinol concentrations in cancer patients
Authors: Peng Yei‐Mei , Dalton William S. , Alberts David S. , Xu Min‐Jian , Lim Heidi , Meyskens Frank L.
Published: February 2007

Concurrent with a phase‐II trial of 4HPR in patients with various cancers, we studied the plasma pharmacokinetics of both 4HPR and its major metabolite 4MPR as well as the effect of 4HPR administration on plasma retinol concentrations using a simple, specific and sensitive HPLC procedure. Initial estimates of plasma pharmacokinetic parameters after oral administration of 4HPR (300 mg/m2) in 3 cancer patients were the following: 4HPR, tβ1/2 = 13.7 hr, AUC = 3.49 μg.hr/ml, CL = 56.57 L/hr/m2; 4MPR, tβ1/2 = 23.0 hr, AUC = 1.15 μg.hr/ml, CL = 239.29 L/hr/m2. We also found that oral administration of 4HPR resulted in a rapid, profound and significant reduction in plasma retinol concentrations. The mean plasma retinol concentrations for 9 patients decreased 60% from baseline to below 200 ng/ml within 1–2 weeks of 4HPR dosing initiation. In addition, there was a concurrent, significant reduction in plasma retinol‐binding protein levels in these patients. The mechanism whereby 4HPR reduces plasma retinol levels in vivo has not been determined. The addition of 4HPR to pooled human plasma at 37°C in vitro did not reduce endogenous retinol levels, suggesting no direct chemical interaction between these 2 retinoids.
Incidence of male breast cancer in scandinavia, 1943–1982
Authors: Ewertz Marianne , Holmberg Lars , Karjalainen Sakari , Tretli Steinar , Adami Hans‐Olov
Published: February 2007

Male breast cancer incidence was examined in a collaborative study of data from the cancer registries in Denmark, Finland, Norway and Sweden, comprising a total of 1,529 cases diagnosed from 1943 to 1982. Effects of age, time of diagnosis, birth cohort and country of residence were evaluated by using statistical models of the multiplicative Poisson type. The logarithm of incidence increased linearly with the logarithm of age and had a slope of about 5. In Denmark, male breast cancer incidence increased significantly with time, about 1% per year. No significant time effects were observed in the other countries. A significant effect of birth cohort appeared in Sweden only, but there was no particular trend in incidence by year of birth. In relation to Denmark, the risk of male breast cancer was lower in Sweden, Norway and Finland, the relative risk estimates with 95% confidence intervals being 0.82(0.72–0.94), 0.72(0.61–0.84) and 0.53(0.43–0.64) respectively. The variation within Scandinavia is similar for female breast cancer, pointing to common factors being involved in the etiology of breast cancer in both sexes.
Human papillomavirus 16 dna in cervical cancers and in lymph nodes of cervical cancer patients: A diagnostic marker for early metastases?
Authors: Fuchs P. G. , Girardi F. , Pfister H.
Published: February 2007

Human papillomavirus (HPV) 16 is most prevalent in cervical cancers and also persists in metastases. We examined HPV16‐DNA‐positive primary cancers and several lymph nodes from each of 14 patients to evaluate the use of HPV16 DNA as a diagnostic marker for the detection of early node involvement. The HPV16 DNA was exclusively integrated in 39% of the primary cancers, predominantly episomal in 36%, and integrated and extrachromosomal to a similar extent in 25%. Thirteen of 16 involved lymph nodes contained HPV16 sequences. Integrated viral DNA showed the same pattern in primary tumors and in metastases. The level of extrachromosomal HPV16 DNA, however, appeared to be considerably reduced in some nodes. HPV16 DNA was also detected in 18 out of 59 histologically negative lymph nodes. This result recommends nucleic acid hybridization as a sensitive method for the detection of HPV‐DNA‐positive cancer cells. The prognostic significance of viral sequences in histologically negative nodes remains to be established.
Relationship between nasopharyngeal carcinoma and high antibody titers to epstein‐barr virus‐specific thymidine kinase
Authors: De Turenne‐Tessier Mireille , Ooka Tadamasa , Calender Alain , De The Guy , Daillie Jacques
Published: February 2007

Epstein‐Barr virus (EBV) has long been implicated in nasopharyngeal carcinoma (NPC). Recent studies in our and other laboratories have shown a correlation between the disease and high antibody titers to EBV specific DNase. These data led us to also examine serial sera from healthy adults and patients with infectious mononucleosis or NPC, for their capacity to neutralize the EBV‐specific thymidine kinase (TK) activity from chemically induced EBV‐carrying human lymphoblastoid cells. Our results were the following: (i) sera were found that efficiently blocked the EBV‐specific TK activity of induced‐Raji TK ‐ cell extracts, but not the host‐cell TK activity from EBV‐negative BJAB cells; (ii) a relationship appeared between high levels of EBV‐specific TK‐neutralizing activity in sera and NPC pathology, even though in this preliminary study the degrees of EBV‐induced TK‐blocking activity detected in sera were not significantly correlated with EBVspecific antibody titers; (iii) the EBV‐induced TK‐neutralizing activity was found in the main lgG fraction derived from NPC sera. These data must be compared with other known antibody responses to EBV for their clinical interest in NPC control.
Soft‐tissue sarcoma, non‐hodgkin's lymphoma and other cancers in new zealand forestry workers
Authors: Reif John , Pearce Neil , Kawachi Ichiro , Fraser James
Published: February 2007

Several studies have suggested that forestry workers are at increased risk for certain types of cancer including soft‐tissue sarcoma (STS) and non‐Hodgkin's lymphoma (NHL). We now report a series of national case‐control studies based on the New Zealand Cancer Registry (NZCR). These involved 19,904 male patients with cancer for the period 1980–1984 who were aged 20 years or more at the time of registration. For each cancer site, the registrations for the remaining sites formed the control group. Current or most recent occupational titles were coded. There was an increased risk for STS (OR = 3.24) in forestry workers which was confined to men under 60 years of age at registration. An elevation in risk for NHL (OR = 1.84) was due to an increase in risk for lymphosarcoma and reticulosarcoma (ICD 200) (OR = 3.18). Acute myeloid leukemia was also associated with forestry work, although the estimate of risk was imprecise (OR = 2.24). Among other cancer sites, an increase in risk of neoplasia of the upper gastro‐intestinal tract (ICD 150, 151, 152) was demonstrated. Odds ratios were elevated for cancer of the esophagus (OR = 1.77), stomach (OR = 2.22), small intestine (OR = 5.22), gall‐bladder (OR = 4.13) and pancreas (OR = 1.79), as well as for nasopharyngeal cancer (OR = 5.56). These increases in cancer risk were not present in sawmill workers in New Zealand during the same period. The factors responsible for the increased cancer risks in forestry workers remain unclear and require further study.
Heterogeneity of antigen expression in benign and malignant breast and ovarian epithelial cells
Authors: Boyer Cinda M. , Borowitz Michael J. , McCarty Kenneth S. , Kinney Robert B. , Everitt Lorri , Dawson Deborah V. , Ring David , Bast Robert C.
Published: February 2007

Expression of II distinct antigen families has been studied in normal and malignant epithelial cells from breast and ovary by avidin‐biotin immunoperoxidase staining of frozen tissue sections. Each of the antigens was expressed in a fraction of the normal and malignant breast tissues from different individuals. Among breast and ovarian cancers, a similar fraction of tumors expressed each of the determinants. An epitope on a 42‐kDa glycoprotein was expressed significantly more often by ovarian carcinomas than by benign ovarian epithelium. Several determinants on 66‐, 240‐kDa or high‐molecular‐weight proteins or glycoproteins were expressed significantly more often on benign breast epithelium than on normal ovarian epithelium. Substantial heterogeneity in antigen expression was observed among different tumor specimens. Each of 14 epithelial ovarian cancers expressed a distinctive combination of antigens. Among 18 breast cancers, 16 distinct antigenic phenotypes were observed. Interestingly, comparable heterogeneity was observed in the expression of epitopes on benign breast and ovarian epithelium, compatible with the possibility that the monoclonal reagents recognized polymorphic determinants. Substantial variations in antigen expression were also observed among cells within each neoplasm. However, when antibodies against 5 different determinants were used in combination, a majority of cells could be stained intensely in all 13 breast carcinomas tested and more than 95% of tumor cells could be stained in 10 of the 13.
The epstein‐barr virus: Host balance in acute infectious mononucleosis patients receiving acyclovir anti‐viral therapy
Authors: Yao Q. Y. , Ogan P. , Rowe M. , Wood M. , Rickinson A. B.
Published: February 2007

This report describes the first of 2 investigations studying mechanisms of Epstein‐Barr virus (EBV) persistence in the infected host; specifically, we wish to determine the extent to which virus carriage within the B‐cell system is dependent upon continued replication of the virus in permissive oropharyngeal epithelium. Levels of EBV infection at these 2 sites have been monitored in 21 acute infectious mononucleosis (IM) patients before, during and after treatment with high doses of acyclovir (ACV). Twelve patients received oral ACV for 10 days and 9 patients received i.v. ACV for 5 days before the 10‐day oral course; all were followed prospectively for 28 days. Infectious EBV, detectable at high initial levels in the patients' throat washings, disappeared almost completely during ACV treatment, then returned again to high levels post treatment. In contrast, levels of virus‐infected B cells in the blood showed no reduction linked to the period of ACV treatment nor any increase with resumption of EBV shedding. During IM, therefore, maintenance of high levels of virus carriage within the B‐cell pool is not dependent upon the continual recruitment of newly infected B cells. This might reflect an inability of the immune T‐cell response in acute IM patients to prevent continued expansion of the existing EBV‐infected B‐cell pool. Alternatively, it raises the possibility that EBV carriage in B cells in vivo is maintained through a virus: cell interaction which is not sensitive to virus‐specific T‐cell surveillance.
Chromosomal aberrations in lymphocytes of patients treated with melphalan
Authors: Mamuris Zissis , Gerbault‐Seureau Michèle , Prieur Marguerite , Pouillart Pierre , Dutrillaux Bernard , Aurias Alain
Published: February 2007

Chromosome lesions detected in lymphocytes from 14 patients previously treated with melphalan, a bifunctional alkylating agent, have been analyzed on R‐banded preparations. In comparison to controls, there was no significant increase of chromatid‐type lesions, but chromosome‐type lesions were quite frequent, affecting 21.5% of metaphases, on the average. Reciprocal translocations represent 54%, unbalanced translocations 15%, deletions 19% and inversions 6% of all rearrangements. Most of these would not have been detected without the use of chromosome banding. The distributions of affected chromosomes and chromosome bands were not random. Almost all imbalances resulting from rearrangements lead to losses but not to gains. The distribution of the abnormal chromosomes has been compared to that observed in controls and in in vitro experiments, and to the characteristic pattern of malignant cells from patients affected by secondary acute leukemia (ANLL).
Extinction of expression of the translocated myc gene in somatic cell hybrids between mouse myeloma and l‐cells
Authors: Greenberg Aviva , Huazzi Mohammad , Sharir Hava , Cohen Lea , Bergman Yehudit , Ber Rosalie , Laskov Reuven
Published: February 2007

Most murine plasma‐cell tumors show a t(12;15) reciprocal chromosomal translocation which truncates the first exon of one of the myc gene alleles and fuses it to one of the switch regions of the immunoglobulin (Ig) heavy‐chain locus. This results in constitutive activation of the translocated myc gene and the production of smaller‐sized mRNA molecules, which are initiated at new sites in the first myc intron. The normal myc allele is not expressed in these myeloma cells. We have studied the expression of the translocated myc gene in somatic cell hybrids between mouse myeloma and L‐cells. Our previous findings show that Ig gene expression is extinguished in such hybrids. In the present work we found that the hybrids contain the normal and translocated myc genes. In contrast to the myeloma parental cells which express the translocated myc gene, the hybrids are similar to the L‐cells in expressing only the normal myc allele. Our results suggest that the L‐cell, fibroblast‐like phenotype, is dominant in these hybrids, and show that the translocated myc gene is expressed in a tissue‐specific manner in the context of the myeloma cell, and is not expressed when subjected to a fibroblast‐like cellular environment.
Drug resistance in kht fibrosarcoma cell lines with different metastatic ability
Authors: Cillo C. , Ling V. , Hill R. P.
Published: February 2007

We have shown previously that tumor cell variants able to form experimental metastases can be generated stochastically in mouse cell lines at high rates and that, in B 16 melanoma cell lines, resistance to drugs is associated with metastatic ability. Recently, we reported on the ability of two lines of KHT fibrosarcoma cells derived from individual experimental lung metastases to generate metastatic variants. The KHT 35L1 cell line maintained a relatively stable high metastatic ability while the parallel line KHT 3L1c possessed a high metastatic ability when first cultured from the lung but rapidly lost this ability and became a line with a metastatic ability similar to the KHT parental line. Subsequent rate analysis indicated that the rate of generation of metastatic variants was higher for KHT 35L1 cells compared to KHT 3L1c or KHT parental cells. Here we examined the ability of these two fibrosarcoma cell lines to generate variants resistant to the drugs methotrexate (MTX) and N‐(phosphonacetyl)‐L‐aspartate (PALA). We observed that the highly metastatic KHT 35L1 cell line is more resistant to these two drugs than the KHT 3L1c or the parental KHT cell lines. Cloning studies indicated that the likely reason for this increased resistance is that the KHT 35L1 cell line generates variants resistant to a given concentration of MTX or PALA at higher rates than the KHT 3L1c or KHT parental cell lines. Since resistance to MTX and PALA usually arises from gene amplification, the results suggest that KHT 35L1 cells possess increased ability to amplify their DNA. The association between the rates of generation of both drug‐resistant and metastatic variants supports the hypothesis that the mechanism of gene amplification may be involved in the generation of both phenotypes.
A phenotypic study of cells from burkitt lymphoma and ebv‐b‐lymphoblastoid lines and their relationship to cells in normal lymphoid tissues
Authors: Ling N. R. , Hardie D. , Lowe J. , Johnson G. D. , Khan M. , Maclennan I. C. M.
Published: February 2007

Cells of 7 EBV‐B‐LCL, 10 Burkitt lines and 13 EBV‐B‐LCL/Burkitt line hybrids have been phenotyped for antigens of the major B cell clusters and for some other antigens. High levels of CD23 and CD39 and low levels of CD38 (T10) were characteristic of EBV‐B‐LCL; the converse was true for Burkitt lines. In hybrids the EBV‐LCL phenotype was dominant. The phenotype of Burkitt‐line cells correlated strongly with that of germinal centre B cells in tonsil sections, but differed markedly from that of marginal zone B cells or follicular mantle cells. The results are discussed in relation to the origin of Burkitt tumours of “sporadic” and “endemic” type, in particular to histopathological evidence that Burkitt lymphomas develop in germinal centres. Recent studies on the location of the breakpoints of Burkitt chromosomal translocations are also considered to be compatible with this concept, even though different regions of the immunoglobulin heavy chain locus are involved in the two types of BL.
Action of recombinant alpha interferon against experimental and spontaneous metastases in a murine model
Authors: Ramani P. , Balkwill F. R.
Published: February 2007

The therapeutic potential of rHuIFN‐α A/D, a hybrid human IFN molecule with equal activity on murine cells, was studied in experimental and spontaneous metastatic models of a murine colon carcinoma COLON 26. rHuIFN‐α A/D inhibited experimental pulmonary metastases of COLON 26 and prolonged the survival of BALB/c mice. Dose scheduling, survival and tumour‐cell clearance studies showed that the first 5 days were critical in the inhibition of pulmonary metastases. However, it is unlikely that lung NK cells were involved in the anti‐metastatic effect of rHuIFN‐α A/D because inhibition of pulmonary metastases and a decrease in radio‐labelled tumour‐cell survival was seen in BALB/c mice depleted selectively of their NK cells by prior treatment with rabbit antiasialoGM1 serum. Although rHuIFN‐α A/D stimulated Nit‐cell activity in BALB/c mice, it was ineffective in abrogating the NK suppressant action of rabbit anti‐asialoGM1 serum on murine lung NK cells. Thus, IFN may mediate its early antimetastatic effect via a mechanism independent of NK‐cell stimulation. IFN also inhibited the development of lung metastases from s.c. COLON 26 tumours in normal, NK‐depleted and T‐cell‐deficient mice.
Selective killing of squamous carcinoma cells by an immunotoxin that recognizes the egf receptor
Authors: Ozawa Soji , Ueda Masakazu , Ando Nobutoshi , Abe Osahiko , Minoshima Shinsei , Shimizu Nobuyoshi
Published: February 2007

We have conjugated a murine monoclonal antibody (B4G7) against the human epidermal growth factor (EGF) receptor to gelonin, a 60S ribosome inactivating protein, via N‐succinimidyl‐3‐(2‐pyridyldithio)propionate (SPDP) and 2‐iminothiolane. The B4G7‐gelonin conjugate bound to the cell surface in proportion to the number of EGF receptors and competed with B4G7 antibody for binding to EGF receptors. The conjugate killed EGF receptor‐hyperproducing squamous carcinoma cells (A431, NA, Ca9‐22, TE5), and to some extent, human fibroblasts (HFO). It did not kill EGF receptor‐deficient small‐cell lung cancer cells (H69) and mouse fibroblasts (Swiss/3T3). Free B4G7, gelonin or a mixture of B4G7 and gelonin did not kill A431 cells. The number of EGF receptors was correlated to cytotoxicity at 10−8 M of the conjugate, and the data were fitted to the regression equation: y = –35.83 log x + 233.4 (correlation coefficient = –0.9995). These results suggest that the B4G7‐gelonin conjugate may be a useful weapon for targeting therapy to squamous‐cell carcinomas.
Effects of activators of protein kinase C, including bryostatins 1 and 2, on the growth of A549 human lung carcinoma cells
Authors: Dale Ian L. , Gescher Andreas
Published: February 2007

Phorbol esters such as 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) inhibit the growth of A549 human lung carcinoma cells at non‐toxic concentrations, whereas 1‐oleoyl‐2‐acetylglycerol and 1,2‐dioctanoylglycerol, synthetic analogues of the physiological ligands of protein kinase C (PKC), do not. Experiments were conducted to test the hypothesis that other activators of PKC are capable of interfering with A549 cell growth. The non‐phorboid tumour promotor mezerein mimicked the growth‐inhibitory effect of TPA in that it arrested growth for 5 days, after which cells proliferated again in the continued presence of the agent. TPA was 20 times more potent as a growth inhibitor than was mezerein. Bryostatin 1 at 10 nM and bryostatin 2 at 100 nM also arrested A549 cell growth and inhibited DNA replication as measured by incorporation of [methyl‐3H]‐thymidine into cells. Inhibition of DNA synthesis to between 90 and 75% of control values developed during the first hour of incubation of the cells with TPA, mezerein or the bryostatins. The extent of inhibition changed little during the subsequent 5 hr of incubation, after which it increased further to reach maximal values within 12 hr. At concentrations above those which caused maximal growth inhibition, the bryostatins abolished both their own inhibition of DNA synthesis and the anti‐replicative effect of TPA and mezerein. The results show that activators of PKC other than phorbol esters are capable of inhibiting the growth of A549 cells. The bryostatins not only interfere with A549 cell growth but can also counter the growth‐inhibitory effect of PKC activators, presumably via interaction with a target separate from the phorbol ester receptor site.
Structure and expression of c‐erbB‐2 and EGF receptor genes in inflammatory and non‐inflammatory breast cancer: Prognostic significance
Authors: Guérin Martine , Gabillot Michèle , Mathieu Marie‐Christine , Travagli Jean‐Paul , Spielmann Marc , Andrieu Nadine , Riou Guy
Published: February 2007

C‐erbB‐2 and epidermal growth factor receptor (EGFR) genes were independently shown to be associated with breast cancer progression. In this report, we have analyzed the structure and expression of these 2 genes in the same tumor specimens of a large series of breast cancers. Two clinical types of tumor were studied: inflammatory (IBC) and non‐inflammatory breast cancers (NBC) obtained from 221 untreated patients at different clinical stages. Amplification and over‐expression of the c‐erbB‐2 proto‐oncogene were observed in 27% and 47% of tumors, respectively, and were strongly associated with breast cancers of the most unfavorable prognosis, namely IBC and NBC with multiple positive axillary nodes. EGFR gene was neither amplified nor rearranged. A restriction fragment length polymorphism (RFLP) for HindIII endonuclease was observed. EGFR transcripts were detected in 46% of tumors and observed more frequently in IBC than in NBC (p < 0.02). In NBC the presence of EGFR transcripts increased linearly with lymph‐node involvement and was associated with estrogen‐receptor‐negative tumors (p = 0.01). Analysis of both genes from the same tumor samples indicated that genes are associated with cancer aggressiveness. Furthermore, in NBC these 2 genes were independently activated, in contrast to IBC in which activated genes were negatively correlated, suggesting that c‐erbB‐2 and EGFR genes play different roles in NBC and IBC.
Immunocytochemical and biochemical analysis of epidermal growth factor receptor expression in human breast cancer tissues: Relationship to estrogen receptor and lymphatic invasion
Authors: Toi M. , Hamada Y. , Nakamura T. , Mukaida H. , Suehiro S. , Wada T. , Toge T. , Niimoto M. , Hattori T.
Published: February 2007

Expression of epidermal growth factor receptor (EGFR) and estrogen receptor (ER) was examined by an immunocytochemical assay (ICA) using serial cross‐sections of human breast cancer tissues. Immunocytochemical results were compared with those obtained by biochemical competitive binding assay and with histological lymphatic invasion. EGFR was evaluated as positive in 17 (34.0%) out of 50 primary tumors by ICA. A significant inverse relationship of the proportion of stained cells between EGFR and ER was demonstrated. In more than one‐half of the tumors that were positive for both EGFR and ER, these 2 receptors were inversely stained in relation to the distribution. In ER‐negative cells, EGFR expression was more marked than in ER‐positive cells. Biochemical data confirmed the immunocytochemical results, pointing to an inverse relationship between EGFR and ER content. EGFR status correlated well with the degree of lymphatic invasion but not with the number of lymph nodes with metastases.
Phenotypic and functional characteristics of tumor‐associated lymphocytes in patients with malignant ascites receiving intraperitoneal infusions of recombinant interleukin‐2 (ril‐2)
Authors: Melioli Giovanni , Baldini Editta , Mingari Maria Cristina , De Maria Andrea , Sertoli Mario Roberto , Badellino Fausto , Percivale Pier Luigi , Catturich Alessandra , Bertoglio Sergio , Civalleri Dario , Santi Leonardo , Moretta Lorenzo
Published: February 2007

In the course of a phase I trial, in which recombinant IL‐2 (riL‐2) was infused intraperitoneally (i.p.) in patients with peritoneal carcinomatosis, we evaluated the effect on “tumorassociated lymphocytes” (TAL) isolated from the ascitic fluid. No major changes in the percentages of cells expressing the CD3, CD4, CD8, Leu‐7, OKM1 and WT‐31 antigens were detected either in TAL or in peripheral blood lymphocytes (PBL) after 7 days of rlL‐2 infusion. In contrast the percentages of TAL (but not PBL) expressing surface IL‐2 receptor (Tac), or LAK‐1 antigen were sharply increased. Analysis of cytolytic functions showed a potentiation of the lytic activity against natural‐killer (NK) sensitive K562 target cells and the de novo appearance of lytic activity against fresh melanoma cells. In one patient IFN‐γ was detected in the ascitic fluid following rIL‐2 infusion. T‐cell clones derived from the patient were analyzed for the IFN‐γ production. While only approximately 40% of PB‐derived control clones produced medium to low amounts of IFN‐γ, all of the TAL‐derived clones produced medium to high amounts of the lymphokine.
Elevated apolipoprotein(A) levels in cancer patients
Authors: Wright Lesley C. , Sullivan David R. , Muller Mark , Dyne Marlen , Tattersall Martin H. N. , Mountford Carolyn E.
Published: February 2007

Elevated plasma lipoprotein(a) has been associated with an increased risk of cardiovascular disease. We report a significant elevation of total plasma apolipoprotein(a) levels in cancer patients compared with hospitalized control patients and normal healthy blood donors. Of the cancer patients studied, 48% had levels in excess of 350 mg/l compared to 20% in normal blood donors and 29% of hospitalized control patients. The elevation was more prevalent but less extreme than that reported in patients with cardiovascular disease. Density gradient centrifugation studies of plasma from cancer patients revealed the presence of apolipoprotein(a) at a density of 1.085 g/ml in the region where mRNA‐containing proteolipids, neoproteolipids and malignancy‐associated lipoproteins had previously been isolated.
Time trends in cancer mortality in the federal republic of germany: Progress against cancer?
Authors: Becker Nikolaus , Smith Elaine M. , Wahrendorf Jürgen
Published: February 2007

In accordance with a previous analysis of US cancer mortality, this report also indicates that cancer mortality in the FRG over the last 3 decades (1952–1985) has not shown any decline commencing in a given period and prevailing in all age groups. If present, such effects could have been interpreted as a manifestation of improvements associated with cancer treatment. The absence of such an effect, derived by using data up to 1985 and age‐specific mortality rates, supports the view expressed in the US analysis that improvements in cancer treatment are unlikely to have an impact on overall cancer mortality statistics and that efforts toward prevention may be more rewarding.
Modelling the risk of adult T‐cell leukemia/lymphoma in persons infected with human T‐lymphotropic virus type I
Authors: Murphy E. L. , Hanchard B. , Figueroa J. P. , Gibbs W. N. , Lofters W. S. , Campbell M. , Goedert J. J. , Blattner W. A.
Published: February 2007

Adult T‐cell leukemia/lymphoma (ATL), a malignancy of mature CD4‐positive lymphocytes, has been etiologically linked to the human retrovirus HTLV‐I. Although a long latent period is suggested from migrant studies, little prospective information on the risk of developing ATL among persons with HTLV‐I infection is available. We present here a model for ATL risk based upon age‐ and sex‐specific HTLV‐I seroprevalence data from a cross‐sectional survey of 13,000 Jamaicans and ATL incidence data from a 21/2‐year case‐control study. By examining the age‐specific incidence of ATL relative to both adult and childhood‐acquired seropositivity versus childhood‐acquired seropositivity alone, we provide evidence in support of the hypothesis that childhood infection with HTLV‐I is important to the development of ATL. Using this model, the cumulative lifetime risk of ATL for those infected before age 20 is estimated to be 4.0% for males and 4.2% for females. Under this hypothesis, HTLV‐I‐associated diseases with shorter latent periods, such as tropical spastic paraparesis, should have a higher incidence in adult females than in adult males.
The significance of oncogene amplification in primary breast cancer
Authors: Seshadri R. , Matthews C. , Dobrovic A. , Horsfall D. J.
Published: February 2007

Alterations in the gene copy numbers of the proto‐oncogenes HER2/neu and c‐myc in primary human breast cancer investigated in 73 patients. We detected amplification of HER2/neu in 17 patient samples and amplification of c‐myc in II, while amplification of both was seen in 6 samples. There was no correlation of age, hormone receptor positivity or tumour size with amplification of either proto‐oncogene. Amplification of HER2/neu was significantly correlated with the stage of the disease. HER2/neu amplification was observed in 18.5% and 38% of node‐negative and node‐positive patients, respectively; the association between HER2/neu amplification and advanced stage of the disease was statistically significant (p = 0.05). Since this is a prospective study, the clinical significance of oncogene amplification is not known. The relatively high frequency of HER2/neu amplification points to a functional role in human breast cancer, particularly in the progression of the disease. The method used in our study allows oncogene amplification to be studied in conjunction with hormone receptor determination and thus may be of value in large clinical trials to determine the significance of oncogene abnormalities in breast cancer.
Delayed‐type hypersensitivity to tumor antigens co‐expressed with immunogenic determinants induced by xenogenization
Authors: Puccetti P. , Bianchi R. , Romani L. , Cenci E. , Fioretti M. C.
Published: February 2007

Previous work has shown that murine lymphoma cells antigenically altered (“xenogenized”) by drug treatment elicit strong in vivo resistance to the original cells. Moreover, splenocytes immune to a drug‐treated variant (L5178Y/DTIC) of a murine lymphoma exert anti‐parental tumor activity in an adoptive transfer system, an effect mediated by L3T4+ lymphocytes and associated with the detection of an anti‐L5178Y delayed‐type hypersensitivity (DTH) response. We now report that the in vivo activity of the tumor‐immune L3T4+ lymphocytes is a radio‐sensitive (2,500 rad in vitro) phenomenon that requires collaboration with radio‐resistant, silicasensitive syngeneic cells in the host, and is inhibited by treatment of recipient mice with monoclonal antibodies (MAbs) to the L3T4 antigen or murine interferon‐gamma (IFN‐γ). In vitro, the tumor‐immune L3T4+ lymphocytes produce interleukin 2 (IL‐2), lymphotoxin (LT) and IFN‐γ activities on incubation with L5178Y cells and spleen‐adherent cells. These results suggest that the mechanisms of anti‐parental tumor protection by xenogenized cells involve specific induction of a DTH response mediated by the “Inflammatory” (THI) subset of L3T4+ T lymphocytes and IFN‐γ activated macrophages.
Monoclonal antibodies to glycolipids of the isoglobo‐series detect tumor‐associated antigens in rats
Authors: Brodin N. Thomas , Thurin Jan , Karlsson Karl‐Anders , Måtensson Stig , Sjögren Hans Olov
Published: February 2007

Monoclonal antibodies (MAbs) directed to 2 neutral glycolipids, isoglobotetraosylceramide and a 6‐sugar isogloboneolactoseries hybrid glycolipid, previously shown to be enriched in rat colorectal tumor tissue, were produced by immunization with purified glycolipids. Four MAbs were selected which demonstrate 3 different specificity patterns when tested for binding to purified and crude preparations of neutral glycolipids, cultured tumor cells and fibroblasts and frozen tissue sections. MAbs 14.2 and 14.10, but not 14.3, stained most epithelial colorectal carcinomas, rat testis and a subpopulation of cells in the rat gastric mucosa. However, all 3 MAbs showed strong staining and binding to sections and cultured clones of the cytokeratin‐negative tumor of colorectal origin, which was originally used for preparation of the glycolipid immunogens. The observed difference between MAbs 14.2/10 and MAb 14.3 could not be explained by differences in binding to the 2 original glycolipids used for screening. However, MAbs 14.2/10 were demonstrated to bind to high‐molecular‐weight glycoprotein(s)(HMW‐gp's) previously shown to carry determinants for syngeneic antibodies and extracted from epithelial colorectal tumor tissue after extensive lipid extraction. This suggests that a protein‐bound carbohydrate determinant, with similarities to the oligosaccharide part of the isoglobo‐series glycolipids, is responsible for this cross‐reactivity. The staining of rat testis could be explained by the strong expression in this tissue of glycolipids with 8–10 sugar residues bound by the 14.2/10 but not 14.3 MAbs. The cell‐surface expression of the 6‐sugar hybrid glycolipid was demonstrated by complement‐dependent cytotoxicity and immunofluorescent staining of viable cells.
Changes in antigen expression on human fme melanoma cells after exposure to hypoxia and acidic ph, alone or in combination
Authors: Davis Catharina De L. , Pettersen Erik O. , Lindmo Tore
Published: February 2007

Quantitative changes in the expression of two tumour‐associated surface antigens on human FME melanoma cells were studied by flow cytometry after exposure to hypoxia and acidic pH, either alone or in combination. The expression of the p250 antigen recognized by the monoclonal antibody (MAb) 9.2.27 was reduced immediately after exposure to hypoxia. The magnitude and duration of the reduction increased with Increasing exposure time. Twelve to 16 hr after the end of a 6‐hr exposure to hypoxia the antigen expression reached the normal level, followed by a temporary increase above this level. The p97a antigen recognized by the 4.1 MAb underwent similar changes after exposure to hypoxia for 6 hr. After exposure to hypoxia in acidic environment, the magnitude and duration of the reduction in the expression of the p250 antigen increased with increasing acidity. The enhancement in antigen expression above the normal level was less after hypoxia at acidic pH than after hypoxia at physiological pH. The combined treatment had an additive effect on the expression of the melanoma‐associated antigen but did not enhance hypoxia‐Induced cell killing. The observed changes in antigen expression might be of importance if hypoxic tumour cells are subjected to MAbs conjugated to radioisotopes or cytotoxic agents for diagnostic or therapeutic purposes.
in vitro thermo‐chemosensitivity screening of spontaneous human tumors: Significant potentiation for cisplatin but not adriamycin
Authors: Calabro Annamaria , Eva Singletary S. , Tucker Susan , Boddie Arthur , Spitzer Gary , Cavaliere Renato
Published: February 2007

The in vitro thermal enhancement of Adriamycin (ADR) and Cisplatin (CDDP) was investigated in 18 surgical biopsy specimens of human tumors cultured in the Adhesive Tumor Cell Culture System. Experimental conditions were adopted to simulate “therapeutic” trials: (a) temperature of 37.0°C, 40.5°C or 42.5°C; (b) hyperthermic duration of 30, 60, or 120 min; and (c) 4‐dose drug range normalized to human bone marrow toxicity. Drug concentrations that inhibited 90% of tumor growth (IC90) at 37.0°C were compared to the IC90 at 40.5°C and 42.5°C, adjusted for the effect of heat alone. CDDP plus heat was a better combination than ADR plus heat, regardless of the temperature and the exposure duration: significant synergism (p < 0.001) occurred in 37% of heat‐CDDP combinations, as compared with 15% of heat‐ADR combinations, and antagonism was significantly lower (p < 0.001) for heat‐CDDP than for heat‐ADR (4.4% versus 21% of combinations, respectively). Within the CDDP group, higher temperature and longer heat exposure resulted in an increased incidence of chemosensitivity. No specific pattern of synergism was evident within the ADR group, but a trend toward a higher incidence of antagonistic effects with increasing hyperthermic duration was observed.
Pregnancy outcomes in childhood cancer survivors: Probable effects of abdominal irradiation
Authors: Hawkins M. M. , Smith R. A.
Published: February 2007

A postal survey addressed to 2,083 general practitioners of childhood cancer survivors of reproductive age has revealed that females having undergone direct abdominal irradiation (exposed), particularly for Wilms' tumour, have an increased risk of several adverse pregnancy outcomes as compared with female survivors of the same types of tumour who had not undergone direct abdominal irradiation (unexposed). Among female survivors, 22% of those exposed and 41% of those unexposed have children. The percentages of first pregnancies reported as ending in spontaneous abortion were 9/40 = 22% (exposed mothers) and 11/174 = 6% (unexposed mothers). The mean birth‐weight of first singleton children born to exposed mothers was over 300 g less than the corresponding value for unexposed mothers. We conclude that radiation is probably involved in the mechanism producing these effects. The findings have implications for counselling survivors, monitoring their pregnancies and treating future patients.
Pancreatic cancer, alcohol, diabetes mellitus and gall‐bladder disease
Authors: Cuzick Jack , Babiker Abdel G.
Published: February 2007

A case‐control study comprising 216 cases of pancreatic cancer and 279 controls was conducted to investigate the relationship of pancreatic cancer with certain chronic medical conditions and with the consumption of tea, coffee and alcoholic beverages. Significant positive associations with preexisting diabetes mellitus and gall‐bladder disease were observed and there was weak evidence of association with liver disease. The relative risks for diabetes mellitus and gallstones diagnosed at least one year previously were 4.1 (p = 0.005) and 2.8 (p = 0.01) respectively. Cases drank significantly more beer than controls (p = 0.005) and there was evidence of a positive trend in risk with total alcohol consumption. Smoking was a clear risk factor, but cases and controls were very similar with respect to tea and coffee drinking habits.
Tissue‐specific expression of a constitutional 3;6 translocation: Development of multiple bilateral renal‐cell carcinomas
Authors: Kovacs Gyula , Brusa Paola , De Riese Werner
Published: February 2007

We describe a German family carrying a constitutional translocation (3;6) (p13;q25.1) in 3 consecutive generations. The only member of the family over 50 years of age and carrying the translocation developed multiple bilateral renal cell carcinomas. We performed chromosome analysis of 4 out of 5 primary tumours, which were characterized by different clonal karyotypes. The constitutionally translocated 3p13‐pter segment was lost with or without the receptor chromosome 6 in each tumour. Additional karyotypic changes were trisomy 5, 7 and 18, monosomy 14 and 21, and loss of the Y chromosome, all karyotype changes occurring frequently in sporadic non‐papillary RCCs. This case is discussed with regard to the possible role of suppressor gene inactivation by constitutional translocation in the development of familial renal cancers.
Amplification of c‐ras‐ki oncogene in human ovarian tumours
Authors: Boltz E. M. , Kefford R. F. , Leary J. A. , Houghton C. R. , Friedlander M. L.
Published: February 2007

Amplification of the c‐ras‐Ki oncogene has been the most consistent finding reported in studies on oncogene activation in ovarian cancer, but for the most part the studies have been small and the results conflicting. In order to determine whether amplification occurred de novo in primary tumours or was associated with tumour progression and metastasis, 81 tumour samples from different sites in 26 patients with ovarian tumours and 7 xenografted ovarian tumour cell lines were assayed. Amplification of c‐ras‐Ki occurred infrequently and was apparent in a single metastatic site in a patient with poorly differentiated serous cystadenocarcinoma of the ovary. Ten‐fold amplification of the c‐ras‐Ki oncogene was also evident in a benign ovarian fibroma. Amplification of the c‐ras‐Ki oncogene is rare in ovarian tumours and does not appear to play a fundamental role in tumour development or progression.
The intracellular association of b700 and b50 murine melanoma antigens and their role in tumor rejection
Authors: Gersten Douglas M. , Williams Laura J. , Moody Dana , Montague Paul M. , Law Lloyd W. , Hearing Vincent J.
Published: February 2007

B700 and B50 are melanoma‐specific antigens originally isolated from B16 murine melanoma. B700, which elicits a strong tumor rejection response, is present on all murine melanomas tested to date. We now demonstrate the presence of B50 in the other murine melanomas and find that the 2 molecules are non‐covalently complexed with each other within the cells. We also show that hosts immunized with intact, irradiated melanoma cells produce antibodies that specifically recognize the B700 and B50 tumor antigens. These results suggest that B50 may also participate in the host response to melanoma growth.
High interferon titer and defective NK‐cell activity in the circulation of nasopharyngeal carcinoma patients
Authors: Lakhdar M. , Oueslati R. , Ellouze R. , Thameur H. , Cammoun M. , Khedhiri N. , Kastally R.
Published: February 2007

The interferon (IFN) activity of sera from 19 patients with nasopharyngeal carcinoma (NPC) was determined by the plaque‐reduction assay with vesicular stomatitis virus (VSV) in HeLa cells and compared to that of sera from matched healthy controls. High titers of interferon were detected in the sera of the NPC patients with a geometric mean titer (GMT) of 43 ± 25 U/ml. The interferon activity of the patients sera was acid‐ and heat‐labile (pH = 2 and 56°C for 1 hr) and could be neutralized by a goat antiserum to human IFN‐γ. Interferon titers of the patients, in contrast, to normal controls, were not correlated with natural killer (NK) activity which was abnormally low in the NPC patients. On the other hand, a high percentage of circulating cells co‐expressing the LGL marker (HNK‐1) and the OKT8 antigen was detected in parallel with high IFN levels in NPC patients.
Testis cancer: Post‐natal hormonal factors, sexual behaviour and fertility
Authors: Swerdlow A. J. , Huttly S. R. A. , Smith P. G.
Published: February 2007

The relationship of risk of testis cancer, and subdivisions of the tumour by histology, to variables which may be related to hormonal status, sexual behaviour and fertility was investigated in data from a case‐control study with 259 cases and 2 sets of controls. No consistent association was found between testis cancer risk and age at puberty, need to shave, obesity, alcohol intake, animal fat intake, and sexual behaviour. There was a significant excess of seminomas in very tall men. Testis cancer cases showed lower fertility than controls according to various measures, but this reflected the greater frequency of cryptorchidism among cases compared to controls. Among non‐cryptorchid subjects there was no clear evidence that infertility was associated with risk of testis cancer.
A case‐control study of multiple myeloma nested in the american cancer society prospective study
Authors: Boffetta P. , Stellman S. D. , Garfinkel L.
Published: February 2007

Among the subjects enrolled in the American Cancer Society Cancer Prevention Study II, a large nation‐wide prospective study, 282 died from multiple myeloma (MM) during the first 4 years of follow‐up. These were divided into incident cases who were initially free from disease and prevalent cases who reported MM or related symptoms at the time of enrollment. For each case, 4 controls matched for age, sex, ethnic group and residence were randomly selected. Previous history of diabetes [odds ratio (OR) = 2.0] and employment as farmer (OR = 2.7) were the risk factors consistently suggested by the results of the analysis. The risk associated with farming showed a linear trend with duration of exposure. Pesticide or herbicide exposure was not a risk factor per se but, when combined with farming, it increased the OR to 4.3. Low education, occupational exposure to dyes, and employment in a bank, on the railroad or as a maid were also suggested risk factors, but either they were not statistically significant or they were based on small numbers of exposed subjects. No association between MM and asbestos exposure was observed.
Lymphokine‐activated killer‐cell function of lymphocytes from peripheral blood, regional lymph nodes and tumor tissues of patients with oral cancer
Authors: Tatake Revati J. , Krishnan Nirmala , Rao R. S. , Fakih A. R. , Gangal Sudha G.
Published: February 2007

Lymphokine‐activated killer (LAK) cells, generated from peripheral blood lymphocytes (PBL) from patients with oral cancer or oral leukoplakia and from healthy donors showed comparable lysis of 6 target tumor cell lines, including 3 derived from head and neck and oral cancers. The tumor burden of the host did not appear to influence the systemic LAK activity. LAK activity of lymphocytes infiltrating the tumor tissues (TIL) was also comparable to that of the PBL. Both TIL and PBL showed a parallel increase in proportion of HNK‐I++ and CD‐25+ CELLS upon activation with IL‐2. The lymph‐node lymphocytes (LNL) from metastatic (met) and non‐metastatic (non‐met) draining lymph nodes, however, showed reduced LAK activity and an increase in CD8 CELLS, in addition to CD25+ and HNK‐I+ cells, when cultured with IL‐2. When IL‐2‐activated LNL were co‐cultured with autologous PBL during IL‐2 activation of the latter, a strong suppressive effect was exerted by LNL In contrast, IL‐2‐activated PBL did not suppress autologous LAK generation in spite of an increase in CD8+ cells seen after activation with IL‐2. Frequency distribution of LAK precursors was significantly lower in LNL than in PBL from oral cancer patients. LAK precursor frequency in TIL was comparable to that of PBL. The results show that, in oral cancer, regional lymph nodes may not have adequate IL‐2‐inducible cytotoxic potential, due to a reduced number of LAK progenitors and possible activation of suppressor cells. Alternatively, TIL can be a potential source for LAK cell function.
The influence of parity and exogenous female hormones on the risk of colorectal cancer
Authors: Davis F. G. , Furner S. E. , Persky V. , Koch M.
Published: February 2007

Evidence that female sex hormones may play a role in the subsequent development of colorectal cancer has accumulated from time trends in colorectal cancer rates and from epidemiologic studies. Using data available from the Cross Cancer Institute Northern Alberta Cancer Program, the relationship of parity, exogenous hormones and colorectal cancer was evaluated. Five hundred and twenty‐eight colon cancer and 192 rectal cancer cases were identified and 349 non‐endocrine cancers were selected as controls. All subjects were diagnosed and interviewed between 1969 and 1973. Protective associations between previous pregnancies and colorectal cancer were found in women over age 50 at diagnosis (OR = 0.5, 95% CI = 0.3–0.9) and in women who never used exogenous hormones (OR = 0.3, 95% CI = 0.2–0.7). Results from this study provide additional support for earlier suggestions that parity may have a protective effect against the development of colorectal cancer, similar to the effects reported in the case of breast, endometrial and ovarian tumors.