- Email: [email protected]
Perhaps not everyone knows that…
880
Prof Heine Hansen Copyright: courtesy of ASCO
... measurement of serum levels of the bone formation marker propeptide of type I procollagen (PINP) can distinguish prostate cancer patients with bone metastasis from those without such metastasis. This is the conclusion of a study from the Cancer Institute Hospital, Tokyo, that measured several bone formation markers in 40 patients without and 25 patients with bone metastasis. Measured markers included PINP, the carboxy-terminal propeptide of type I procollagen (PICP), bone-specific alkaline phosphatase (BALP), and bone Gla protein (BGP), a bone resorption marker (pyridinoline cross-linked carboxy-terminal telopeptide, ICTP), and prostate specific antigen (PSA). All except BGP were significantly higher in patients with bone metastasis than in those without, with levels of PINP showing correlation with the extent of disease [1]. ... dendritic cells transfected with PCR-amplified prostate cancer RNA are capable of stimulating polyclonal, cancer-specific cytotoxic T-lymphocyte (CTL) responses. Although dendritic cells pulsed with single prostate-cancer-specific antigens are known to stimulate strong CTL responses there has been a concern that tumour cell mutation could lead to the loss of the antigen from cells. A group from Duke University Medical Center has sought to eliminate this concern by transfecting RNA amplified from biopsies to generate polyclonal responses to a broad range of prostate cancer antigens. The responses generated encompassed, as subcomponents, responses against PSA and telomerase reverse transcriptase. However, the tumour-specific CTL were consistently more effective than PSA CTL or telomerase reverse transcriptase CTL in lysing tumor targets, suggesting the superiority of the polyclonal response [2]. ...thoracoscopic/laparoscopic (TS/LS) staging of oesophageal cancer is feasible and can increase the number of positive lymph nodes identified. This is the conclu-
...the degree of immunosuppression experienced by HIV-infected women may contribute to the development of cervical intraepithelial lesions, but once a lesion is established disease progression may not be affected by CD4+ counts. These are the conclusions of a study from Albert Einstein College of Medicine, Bronx, that aimed to examine the association between cervicovaginal smears from HIV-infected women and their CD4+ counts and HIV viral load. The study reviewed 296 cervicovaginal smears from 108 HIV-infected and classified them according to the Bethesda system. Abnormal cytologies (n = 74) were followed by colposcopy and/or biopsy. CD4+ counts and HIV viral loads were available at the time of the cytologic evaluation. The control group (without cervical lesions, n = 222) had significantly higher CD4+ counts (378 cells/jal vs. 246 cells/ul; P < 0.001) compared with the group with cervical lesions, buhere was no difference between the CD4+ counts from women with low-grade lesions and those from women with high-grade lesions. Viral load was significantly higher in patients with cytologic abnormalities than in those with negative Papanicolaou smears (P = 0.006) [4]. ...postgraft administration of granulocyte colonystimulating factor (G-CSF) impairs functional immune recovery in recipients of human leukocyte antigen haplotype-mismatched hematopoietic transplants. Moreover, G-CSF does not improve engraftment. In a study from the Department of Clinical and Experimental Medicine, University of Perugia, 43 patients with acute leukemia receiveing G-CSF after transplantation showed an engraftment rate of 95%. However, the patients had a long-lasting type 2 immune reactivity, i.e., T-helper-2-inducing dendritic cells not producing interleukin 12 (IL-12) and high frequencies of IL-4-producing and IL-10-producing CD4(+) cells not expressing the IL-12 receptor (3(2) chain. Similar reactivity patterns were observed on exposure of donor cells to
Downloaded from http://annonc.oxfordjournals.org/ by guest on March 23, 2016
Perhaps not everyone knows that...
sion of a prospective Intergroup NCI trial that recruited 134 patients between 1995 and 1999. The authors report that the lymph node stations most frequently sampled were, in the thorax (134 patients), levels 2 (33%), 3 (38%), 4 (40%), 7 (76%), 8 (69%), 9 (55%), and 10 (43%) and, in the abdomen, levels 17 (70%) and 20 (55%). The frequency of positive nodes by level were as follows: 2 (10%), 3 (8%), 4 (10%), 7 (10%), 8 (25%), 9 (10%), 10 (10%), 17 (34%), and 20 (27%). CTscans, MRI and oesophageal ultrasound scan each incorrectly identified TN staging as noted by missed positive or false-negative nodes or metastatic disease found at TS/LS staging in 50%, 40%, and 30% of patients, respectively. Although the criteria for feasibility were met, the overall accuracy remains to be defined by analysis of the lymph node-negative group in follow-up, and the authors call for further study to confirm the role of TS/LS in the staging algorithm of oesophageal cancer [3].
881 G-CSF. A subsequent series of 36 patients with acute leukemia not receiving G-CSF after engraftment showed no adverse affect on engraftment rate (93%), the anticipated appearance of IL-12-producing dendritic cells (1-3 months after transplantation vs. > 12 months in transplant recipients given G-CSF), CD4(+) cells of a mixed ThO/Th1 phenotype, and of antifungal T-cell reactivity in vitro. In addition, CD4(+) cell counts increased in significantly less time. There was no significant increase in the incidence of graft-versushost disease with the elimination of G-CSF [5].
...nitrate contamination of drinking water may increase cancer risk, because nitrate is endogenously reduced to nitrite and subsequent nitrosation reactions produce N-nitroso compounds which are highly carcinogenic and can act systemically. Moreover, the increased risk extends not only to bladder cancer, as has been previously suggested, but also to ovarian cancers. These are among the conclusions of a study from the Center for Health Effects of Environmental Contamination, University of Iowa, in which the cancer incidence in a cohort of 21 977 Iowa women aged 55-69 years in 1986 and had used the same water supply more than 10 years (87% > 20 years), nitrate exposure from 1955 to 1988 was assessed using public databases for municipal water supplies in Iowa (quartile cut-off points: 0.36, 1.01, and 2.46 mg/liter nitratenitrogen) with each woman assigned an average level of exposure calculated on a community basis. Cancer incidence (n = 3150 cases) from 1986 to1998 was assessed by linkage to the Iowa Cancer Registry. The study found positive associations for bladder cancer [relative risks (RRs) across nitrate quartiles = 1, 1.69, 1.10, and 2.83] and ovarian cancer (RR = 1, 1.52, 1.81, and 1.84) after adjustment for a variety of cancer risk/ protective factors [7].
...the binding of paclitaxel to (3-tubulin has been shown, by crystallographic studies, to involve a previously unpredicted T-shaped or butterfly paclitaxel structure. Although the antitumour activity of paclitaxel is known to be due to its ability to stabilise microtubules by binding to (3-tubulin, the original data were insufficient to make an absolute determination of the bound conformation. Researchers from Emory University Department of Chemistry have now correlated the crystallographic density with analysis of a number of paclitaxel conformations and have found the unique solution to be a T-shaped paclitaxel structure. In contrast to previous models, in which it was predicted that the hydrophobic groups of paclitaxel would associate with each other, the new model has these groups interacting with the protein. The authors suggest that this model provides structural rationalization for much of the available paclitaxel structure-activity relationship data, including acquired paclitaxel resistance occurring by (3-tubulin mutation in human cancer cells [9]. ...although it is recognised as a first-line tool for retrieving biomedical information, Medline may now also serve as a tool for discovering new connections between particular genes and biological processes. The US National Library of Medicine's Medline citation database is the world's largest searchable collection of biomedical literature and has, since 1966, accumulated more than 11 million titles and abstracts from articles published in over 4000 relevant journals. Now a Norwegian group has outlined a computational ap-
Downloaded from http://annonc.oxfordjournals.org/ by guest on March 23, 2016
... doses of opiods and sedatives given to terminally ill cancer patients do not affect survival during the last 48 hours of life. This is the conclusion of a prospective study, from Seirei Mikatabara Hospital, Shizuoka, Japan, in which patient characteristics and clinical symptoms of 209 hospice inpatients were recorded. Information about opioid and sedative use in the last two days of life was also collected by a chart review. 82% of the patients received opioids, with a median dose of 80 mg oral morphine equivalent (OME)/48 h, while 60% received some sedative medications, mainly haloperidol (43% of total sample, 7.5 mg/48 h), midazolam (23%, 23 mg/48 h), and hydroxyzine (15%, 50 mg/48 h). There were no significant differences in survival between the patients who received different doses of opioids ( < 240, 240-599, and > 600 mg OME/ 48 h) and of benzodiazepines (0, 1-59, and ^ 6 0 mg parental midazolam equivalent/48 h). The survival of patients who received haloperidol, hydroxyzine, and other sedative medications did not differ from those who did not [6].
...the age, sex, and housing conditions of European smokers participating in smoking cessation programmes have major effects on the outcomes of these programmes. These are the conclusions of a recent analysis of data from 3575 smokers who participated in the Collaborative European Anti-smoking Evaluation (CEASE) trial, a multicentred study that used transdermal nicotine patches as an adjunct to smoking cessation in the chest clinic. In the analysis, logistic regression modelling was used to assess the effects of age, sex, smoking habit, socioeconomic status (housing conditions, education, and employment), disease, smoking habits of relatives, and baseline markers of tobacco use on sustained smoking cessation (selfreported abstinence and expired carbon monoxide <10 parts per million). An effect of treatment on smoking cessation was observed (OR = 1.50; 95% confidence interval (95% Cl): 1.15-1.96), with additional effects on outcome being seen for age (OR = 1.02; 95% Cl: 1.01-1.03), sex (men vs. women: OR = 1.38; 95% Cl: 1.14-1.68), housing conditions (OR = 1.43; 95% Cl: 1.25-1.65), current respiratory (OR = 0.79; 95% Cl: 0.67-0.92) or cardiac disease (OR = 0.46; 95% Cl: 0.28-0.75), and markers of tobacco use (cigarettes/day: OR = 0.79; 95% Cl: 0.69-0.90. expired carbon monoxide: OR = 0.98; 95% Cl: 0.97-0.99) [8].
882 proach to extracting new information from this massive archive. Conducted on a large scale across the entire database, the analysis generates networks of related genes that reveal previously unknown aspects of biology. A similar, if smaller scale, approach was published last year by researchers from the Kentucky Center for Structural Biology, University of Kentucky, who coined the term 'biobibliometrics' [10].
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References 11. 1. Koizumi M, Yonese J, Fukui I, Ogata E. The serum level of the amino-terminal propeptide of type I procollagen is a sensitive
Downloaded from http://annonc.oxfordjournals.org/ by guest on March 23, 2016
...The basic assumption is that genes that are mentioned in the same abstract are likely to have a biological relationship. By analogy to global approaches to understanding the genome and proteome, the Norwegian group have now searched the titles and abstracts of over 10 million Medline citations - the 'biobibliome' - to produce a 'gene-to-gene co-citation network' for 13 712 known human genes. By annotating this network with biological attributes such as medical subject heading (MeSH) terms, the authors have identified meaningful biological relationships between sets of genes that, although they had not been predicted, were subsequently validated by experimentation. The computational tools to carry out these analyses have been deposited in a publicly available database called PubGene (http://www.PubGene.org) [11].
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marker for prostate cancer metastasis to bone BJU Int 2001; 87: 348-51. Heiser A, Maurice MA, Yancey DR et al Induction of polyclonal prostate cancer-specific CTL using dendritic cells transfected with amplified tumor RNA. J Immunol 2001; 166: 2953-60 Krasna MJ, Reed CE, Nedzwiecki D et al. CALGB 9380: A prospective trial of the feasibility of thoracoscopy/laparoscopy in staging esophageal cancer. Ann Thorac Surg 2001; 71. 1073-9 Cardillo M, Hagan R, Abadi J, Abadi MA. CD4 T-cell count, viral load, and squamous intraepithelial lesions in women infected with the human immunodeficiency virus. Cancer 2001; 93: 111-4. Volpi I, Perruccio K, Tosti A et al. Postgrafting administration of granulocyte colony-stimulating factor impairs functional immune recovery in recipients of human leukocyte antigen haplotype-mismatched hematopoietic transplants. Blood 2001; 97 2514-21. Morita T, Tsunoda J, Inoue S, Chihara S. Effects of high dose opioids and sedatives on survival in terminally ill cancer patients. J Pain Symptom Manage 2001, 21: 282-9. Weyer PJ, Cerhan JR, Kross BC et al. Municipal drinking water nitrate level and cancer risk in older women: The Iowa Women's Health Study Epidemiology 2001; 12- 327-38. Monso E, Campbell J, Tonnesen P et al. Sociodemographic predictors of success in smoking intervention. Tob Control 2001;10.165-9 Snyder JP, Nettles JH, Cornett B et al The binding conformation of Taxol in beta-tubulin: A model based on electron crystallography density. Proc Natl Acad Sci USA 2001, 98: 5312-6. Stapley BJ, BenoitG. Biobibliometrics Information retrieval and visualization from co-occurrences of gene names in Medline abstracts. Pac Symp Biocomput 2000; 29-40. Jenssen TK, Laegreid A, Komorowski J, Hovig E. A literature network of human genes for high-throughput analysis of gene expression. Nat Genet 2001; 28: 21-8.
Prof Heine Hansen Copyright: courtesy of ASCO
... measurement of serum levels of the bone formation marker propeptide of type I procollagen (PINP) can distinguish prostate cancer patients with bone metastasis from those without such metastasis. This is the conclusion of a study from the Cancer Institute Hospital, Tokyo, that measured several bone formation markers in 40 patients without and 25 patients with bone metastasis. Measured markers included PINP, the carboxy-terminal propeptide of type I procollagen (PICP), bone-specific alkaline phosphatase (BALP), and bone Gla protein (BGP), a bone resorption marker (pyridinoline cross-linked carboxy-terminal telopeptide, ICTP), and prostate specific antigen (PSA). All except BGP were significantly higher in patients with bone metastasis than in those without, with levels of PINP showing correlation with the extent of disease [1]. ... dendritic cells transfected with PCR-amplified prostate cancer RNA are capable of stimulating polyclonal, cancer-specific cytotoxic T-lymphocyte (CTL) responses. Although dendritic cells pulsed with single prostate-cancer-specific antigens are known to stimulate strong CTL responses there has been a concern that tumour cell mutation could lead to the loss of the antigen from cells. A group from Duke University Medical Center has sought to eliminate this concern by transfecting RNA amplified from biopsies to generate polyclonal responses to a broad range of prostate cancer antigens. The responses generated encompassed, as subcomponents, responses against PSA and telomerase reverse transcriptase. However, the tumour-specific CTL were consistently more effective than PSA CTL or telomerase reverse transcriptase CTL in lysing tumor targets, suggesting the superiority of the polyclonal response [2]. ...thoracoscopic/laparoscopic (TS/LS) staging of oesophageal cancer is feasible and can increase the number of positive lymph nodes identified. This is the conclu-
...the degree of immunosuppression experienced by HIV-infected women may contribute to the development of cervical intraepithelial lesions, but once a lesion is established disease progression may not be affected by CD4+ counts. These are the conclusions of a study from Albert Einstein College of Medicine, Bronx, that aimed to examine the association between cervicovaginal smears from HIV-infected women and their CD4+ counts and HIV viral load. The study reviewed 296 cervicovaginal smears from 108 HIV-infected and classified them according to the Bethesda system. Abnormal cytologies (n = 74) were followed by colposcopy and/or biopsy. CD4+ counts and HIV viral loads were available at the time of the cytologic evaluation. The control group (without cervical lesions, n = 222) had significantly higher CD4+ counts (378 cells/jal vs. 246 cells/ul; P < 0.001) compared with the group with cervical lesions, buhere was no difference between the CD4+ counts from women with low-grade lesions and those from women with high-grade lesions. Viral load was significantly higher in patients with cytologic abnormalities than in those with negative Papanicolaou smears (P = 0.006) [4]. ...postgraft administration of granulocyte colonystimulating factor (G-CSF) impairs functional immune recovery in recipients of human leukocyte antigen haplotype-mismatched hematopoietic transplants. Moreover, G-CSF does not improve engraftment. In a study from the Department of Clinical and Experimental Medicine, University of Perugia, 43 patients with acute leukemia receiveing G-CSF after transplantation showed an engraftment rate of 95%. However, the patients had a long-lasting type 2 immune reactivity, i.e., T-helper-2-inducing dendritic cells not producing interleukin 12 (IL-12) and high frequencies of IL-4-producing and IL-10-producing CD4(+) cells not expressing the IL-12 receptor (3(2) chain. Similar reactivity patterns were observed on exposure of donor cells to
Downloaded from http://annonc.oxfordjournals.org/ by guest on March 23, 2016
Perhaps not everyone knows that...
sion of a prospective Intergroup NCI trial that recruited 134 patients between 1995 and 1999. The authors report that the lymph node stations most frequently sampled were, in the thorax (134 patients), levels 2 (33%), 3 (38%), 4 (40%), 7 (76%), 8 (69%), 9 (55%), and 10 (43%) and, in the abdomen, levels 17 (70%) and 20 (55%). The frequency of positive nodes by level were as follows: 2 (10%), 3 (8%), 4 (10%), 7 (10%), 8 (25%), 9 (10%), 10 (10%), 17 (34%), and 20 (27%). CTscans, MRI and oesophageal ultrasound scan each incorrectly identified TN staging as noted by missed positive or false-negative nodes or metastatic disease found at TS/LS staging in 50%, 40%, and 30% of patients, respectively. Although the criteria for feasibility were met, the overall accuracy remains to be defined by analysis of the lymph node-negative group in follow-up, and the authors call for further study to confirm the role of TS/LS in the staging algorithm of oesophageal cancer [3].
881 G-CSF. A subsequent series of 36 patients with acute leukemia not receiving G-CSF after engraftment showed no adverse affect on engraftment rate (93%), the anticipated appearance of IL-12-producing dendritic cells (1-3 months after transplantation vs. > 12 months in transplant recipients given G-CSF), CD4(+) cells of a mixed ThO/Th1 phenotype, and of antifungal T-cell reactivity in vitro. In addition, CD4(+) cell counts increased in significantly less time. There was no significant increase in the incidence of graft-versushost disease with the elimination of G-CSF [5].
...nitrate contamination of drinking water may increase cancer risk, because nitrate is endogenously reduced to nitrite and subsequent nitrosation reactions produce N-nitroso compounds which are highly carcinogenic and can act systemically. Moreover, the increased risk extends not only to bladder cancer, as has been previously suggested, but also to ovarian cancers. These are among the conclusions of a study from the Center for Health Effects of Environmental Contamination, University of Iowa, in which the cancer incidence in a cohort of 21 977 Iowa women aged 55-69 years in 1986 and had used the same water supply more than 10 years (87% > 20 years), nitrate exposure from 1955 to 1988 was assessed using public databases for municipal water supplies in Iowa (quartile cut-off points: 0.36, 1.01, and 2.46 mg/liter nitratenitrogen) with each woman assigned an average level of exposure calculated on a community basis. Cancer incidence (n = 3150 cases) from 1986 to1998 was assessed by linkage to the Iowa Cancer Registry. The study found positive associations for bladder cancer [relative risks (RRs) across nitrate quartiles = 1, 1.69, 1.10, and 2.83] and ovarian cancer (RR = 1, 1.52, 1.81, and 1.84) after adjustment for a variety of cancer risk/ protective factors [7].
...the binding of paclitaxel to (3-tubulin has been shown, by crystallographic studies, to involve a previously unpredicted T-shaped or butterfly paclitaxel structure. Although the antitumour activity of paclitaxel is known to be due to its ability to stabilise microtubules by binding to (3-tubulin, the original data were insufficient to make an absolute determination of the bound conformation. Researchers from Emory University Department of Chemistry have now correlated the crystallographic density with analysis of a number of paclitaxel conformations and have found the unique solution to be a T-shaped paclitaxel structure. In contrast to previous models, in which it was predicted that the hydrophobic groups of paclitaxel would associate with each other, the new model has these groups interacting with the protein. The authors suggest that this model provides structural rationalization for much of the available paclitaxel structure-activity relationship data, including acquired paclitaxel resistance occurring by (3-tubulin mutation in human cancer cells [9]. ...although it is recognised as a first-line tool for retrieving biomedical information, Medline may now also serve as a tool for discovering new connections between particular genes and biological processes. The US National Library of Medicine's Medline citation database is the world's largest searchable collection of biomedical literature and has, since 1966, accumulated more than 11 million titles and abstracts from articles published in over 4000 relevant journals. Now a Norwegian group has outlined a computational ap-
Downloaded from http://annonc.oxfordjournals.org/ by guest on March 23, 2016
... doses of opiods and sedatives given to terminally ill cancer patients do not affect survival during the last 48 hours of life. This is the conclusion of a prospective study, from Seirei Mikatabara Hospital, Shizuoka, Japan, in which patient characteristics and clinical symptoms of 209 hospice inpatients were recorded. Information about opioid and sedative use in the last two days of life was also collected by a chart review. 82% of the patients received opioids, with a median dose of 80 mg oral morphine equivalent (OME)/48 h, while 60% received some sedative medications, mainly haloperidol (43% of total sample, 7.5 mg/48 h), midazolam (23%, 23 mg/48 h), and hydroxyzine (15%, 50 mg/48 h). There were no significant differences in survival between the patients who received different doses of opioids ( < 240, 240-599, and > 600 mg OME/ 48 h) and of benzodiazepines (0, 1-59, and ^ 6 0 mg parental midazolam equivalent/48 h). The survival of patients who received haloperidol, hydroxyzine, and other sedative medications did not differ from those who did not [6].
...the age, sex, and housing conditions of European smokers participating in smoking cessation programmes have major effects on the outcomes of these programmes. These are the conclusions of a recent analysis of data from 3575 smokers who participated in the Collaborative European Anti-smoking Evaluation (CEASE) trial, a multicentred study that used transdermal nicotine patches as an adjunct to smoking cessation in the chest clinic. In the analysis, logistic regression modelling was used to assess the effects of age, sex, smoking habit, socioeconomic status (housing conditions, education, and employment), disease, smoking habits of relatives, and baseline markers of tobacco use on sustained smoking cessation (selfreported abstinence and expired carbon monoxide <10 parts per million). An effect of treatment on smoking cessation was observed (OR = 1.50; 95% confidence interval (95% Cl): 1.15-1.96), with additional effects on outcome being seen for age (OR = 1.02; 95% Cl: 1.01-1.03), sex (men vs. women: OR = 1.38; 95% Cl: 1.14-1.68), housing conditions (OR = 1.43; 95% Cl: 1.25-1.65), current respiratory (OR = 0.79; 95% Cl: 0.67-0.92) or cardiac disease (OR = 0.46; 95% Cl: 0.28-0.75), and markers of tobacco use (cigarettes/day: OR = 0.79; 95% Cl: 0.69-0.90. expired carbon monoxide: OR = 0.98; 95% Cl: 0.97-0.99) [8].
882 proach to extracting new information from this massive archive. Conducted on a large scale across the entire database, the analysis generates networks of related genes that reveal previously unknown aspects of biology. A similar, if smaller scale, approach was published last year by researchers from the Kentucky Center for Structural Biology, University of Kentucky, who coined the term 'biobibliometrics' [10].
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References 11. 1. Koizumi M, Yonese J, Fukui I, Ogata E. The serum level of the amino-terminal propeptide of type I procollagen is a sensitive
Downloaded from http://annonc.oxfordjournals.org/ by guest on March 23, 2016
...The basic assumption is that genes that are mentioned in the same abstract are likely to have a biological relationship. By analogy to global approaches to understanding the genome and proteome, the Norwegian group have now searched the titles and abstracts of over 10 million Medline citations - the 'biobibliome' - to produce a 'gene-to-gene co-citation network' for 13 712 known human genes. By annotating this network with biological attributes such as medical subject heading (MeSH) terms, the authors have identified meaningful biological relationships between sets of genes that, although they had not been predicted, were subsequently validated by experimentation. The computational tools to carry out these analyses have been deposited in a publicly available database called PubGene (http://www.PubGene.org) [11].
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marker for prostate cancer metastasis to bone BJU Int 2001; 87: 348-51. Heiser A, Maurice MA, Yancey DR et al Induction of polyclonal prostate cancer-specific CTL using dendritic cells transfected with amplified tumor RNA. J Immunol 2001; 166: 2953-60 Krasna MJ, Reed CE, Nedzwiecki D et al. CALGB 9380: A prospective trial of the feasibility of thoracoscopy/laparoscopy in staging esophageal cancer. Ann Thorac Surg 2001; 71. 1073-9 Cardillo M, Hagan R, Abadi J, Abadi MA. CD4 T-cell count, viral load, and squamous intraepithelial lesions in women infected with the human immunodeficiency virus. Cancer 2001; 93: 111-4. Volpi I, Perruccio K, Tosti A et al. Postgrafting administration of granulocyte colony-stimulating factor impairs functional immune recovery in recipients of human leukocyte antigen haplotype-mismatched hematopoietic transplants. Blood 2001; 97 2514-21. Morita T, Tsunoda J, Inoue S, Chihara S. Effects of high dose opioids and sedatives on survival in terminally ill cancer patients. J Pain Symptom Manage 2001, 21: 282-9. Weyer PJ, Cerhan JR, Kross BC et al. Municipal drinking water nitrate level and cancer risk in older women: The Iowa Women's Health Study Epidemiology 2001; 12- 327-38. Monso E, Campbell J, Tonnesen P et al. Sociodemographic predictors of success in smoking intervention. Tob Control 2001;10.165-9 Snyder JP, Nettles JH, Cornett B et al The binding conformation of Taxol in beta-tubulin: A model based on electron crystallography density. Proc Natl Acad Sci USA 2001, 98: 5312-6. Stapley BJ, BenoitG. Biobibliometrics Information retrieval and visualization from co-occurrences of gene names in Medline abstracts. Pac Symp Biocomput 2000; 29-40. Jenssen TK, Laegreid A, Komorowski J, Hovig E. A literature network of human genes for high-throughput analysis of gene expression. Nat Genet 2001; 28: 21-8.