bluuebunny/crossref_metadata_2025_split 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

AbstractConcurrent 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

AbstractMale 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

AbstractHuman 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

AbstractEpstein‐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

AbstractSeveral 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

AbstractExpression 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

AbstractThis 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

AbstractChromosome 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

AbstractMost 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

AbstractWe 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

AbstractCells 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

AbstractThe 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

AbstractWe 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

AbstractPhorbol 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

AbstractC‐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

AbstractExpression 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.