bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer in Greenlandic Inuit 1973–1997: A cohort study
Authors: Friborg Jeppe , Koch Anders , Wohlfarht Jan , Storm Hans‐Henrik , Melbye Mads 
Published: January 2004

AbstractThe increasing westernization of the Arctic countries may influence the very particular cancer profile of these populations. Our objective was to investigate the development in cancer incidence from 1973 to 1997 in a large and well‐defined Inuit population in Greenland. Greenland is part of the Danish Kingdom, and population statistics covering both countries are available from the same registry resource. Data from the Danish Civil Registration System and from the Danish Cancer Registry were used to calculate age‐standardized cancer incidence rates for the periods 1973–1987 and 1988–1997 for persons born in Greenland. Using rates for Denmark, sex‐specific standardized incidence ratios (SIRs) for 1988–1997 were calculated. Furthermore, age‐ and sex‐specific incidence rates in the 2 periods were calculated for selected cancers. Total cancer incidence increased from 248.5 to 277.9 per 100,000 person‐years in men and from 269.4 to 302.2 per 100,000 person‐years in women. The incidence of lung, stomach, breast and colon cancer increased, whereas the incidence of cervical cancer decreased. Compared to the Caucasian population in Denmark, high SIRs were found for cancers of the nasopharynx, salivary gland, esophagus, stomach and cervix and low SIRs for testis, bladder, prostate, breast and hematologic cancers. Overall cancer incidence among Greenlandic Inuit is increasing as a result of increases in several cancers that are common in Western populations. A significant increase in the incidence of stomach cancer in both sexes, which contrasts global trends for this cancer, warrants further investigation. © 2003 Wiley‐Liss, Inc.
Selective and nonselective toxicity of TRAIL/Apo2L combined with chemotherapy in human bone tumour cells vs. normal human cells
Authors: Van Valen Frans , Fulda Simone , Schäfer Karl‐Ludwig , Truckenbrod Borna , Hotfilder Marc , Poremba Christopher , Debatin Klaus‐Michael , Winkelmann Winfried 
Published: January 2004

AbstractAlthough TRAIL/Apo2L preferably induces apoptosis in tumour cells without toxicity in normal cells, many tumour cell types display TRAIL/Apo2L resistance. Whether TRAIL/Apo2L in combination with chemotherapy may overcome TRAIL/Apo2L resistance while maintaining tumour selectivity remains to be determined. Here, we report that while ActD, DOX and CDDP sensitised both OS and Ewing's tumour cell lines and normal cells (hOBs, synovial cells, fibroblasts) to TRAIL/Apo2L‐induced apoptosis, the combination of etoposide (VP16) and TRAIL/Apo2L was selectively active on tumour cells without affecting normal cells. Sensitisation of OS cells and hOBs to TRAIL/Apo2L did not correlate with a compatible change in the gene expression profile of the receptors for TRAIL/Apo2L determined by quantitative real‐time RT‐PCR. Also, sensitisation of the TRAIL/Apo2L death pathway did not rely entirely on the chemotherapy‐induced, caspase‐dependent cytotoxicity. Further, chemotherapy did not cause a compatible change in expression levels of proteins such as Bcl‐2, Bcl‐xL, Bax, cIAP2, XIAP and survivin. However, ActD, DOX and CDDP downregulated expression of cFLIP in OS cells as well as expression of p21 in normal hOBs. Interestingly, while VP16 also extinguished cFLIP in OS cells, which were sensitised for TRAIL/Apo2L by VP16, VP16 induced cFLIP and enhanced p21 levels in normal hOBs, which remained refractory to VP16 plus TRAIL/Apo2L. Together, our data reveal that TRAIL/Apo2L combined with certain chemotherapeutic drugs is toxic to bone tumour and normal human cells and suggest that cotreatment with TRAIL/Apo2L and VP16 provides an attractive approach for selective killing of tumour cells while leaving unaffected normal cells. © 2003 Wiley‐Liss, Inc.
The association between stressful life events and breast cancer risk: A meta‐analysis
Authors: Duijts Saskia F.A. , Zeegers Maurice P.A. , Borne Bart Vd 
Published: January 2004

AbstractBreast cancer is the most prevalent cancer in women in Western societies. Studies examining the relationship between stressful life events and breast cancer risk have produced conflicting results. The purpose of this meta‐analysis was to identify studies on this relationship, between 1966 and December 2002, to summarize and quantify the association and to explain the inconsistency in previous results. Summary odds ratios and standard errors were calculated, using random effect meta‐regression analyses, for the following categories: stressful life events, death of spouse, death of relative or friend, personal health difficulties, nonpersonal health difficulties, change in marital status, change in financial status and change in environmental status. The presence of publication bias has been explored, and sensitivity analyses were performed to identify heterogeneity, using calculation of the percentage of variability due to heterogeneity, meta‐regression analyses and stratification. Only the categories stressful life events (OR = 1.77, 95% CI 1.31–2.40), death of spouse (OR = 1.37, 95% CI 1.10–1.71) and death of relative or friend (OR = 1.35, 95% CI 1.09–1.68) showed a statistically significant effect. Publication bias was identified in both stressful life events (p = 0.00) and death of relative or friend (p = 0.02). Sensitivity analyses resulted in the identification of heterogeneity in all categories, except death of spouse. The results of this meta‐analysis do not support an overall association between stressful life events and breast cancer risk. Only a modest association could be identified between death of spouse and breast cancer risk. © 2003 Wiley‐Liss, Inc.
Estimation of the potential for nitrosation and its inhibition in subjects from high‐ and low‐risk areas for esophageal cancer in southern China
Authors: Lin Kun , Shen Wenying , Shen Zhongying , Cai Shushen , Wu Yongning 
Published: January 2004

AbstractWe studied 2 counties in southern China, which are close to each other but show very different mortality rates from esophageal cancer. We collected 12 hr urine samples and analyzed them for NPRO, other nitrosamino acids, nitrate and ASC. The potential for forming NPRO and the effect on inhibition by ASC were recorded. Urine was collected after (i) no treatment, (ii) a dose of proline and (iii) proline with ASC. Intake and excretion of nitrate were significantly greater in the high‐risk area. After the proline dose, urinary excretion of NPRO was significantly greater in the high‐risk area. The inhibitory effect of ASC after taking it with proline was less in the high‐risk area. Hence, the high‐risk area showed greater potential for forming NPRO, and this formation was less inhibited by ASC. This supports the view that esophageal cancer in this area may be caused by nitrosamines formed in vivo, perhaps from nitrite produced by reduction of ingested nitrate. © 2003 Wiley‐Liss, Inc.
Intensified oxidative and nitrosative stress following combined ALA‐based photodynamic therapy and local hyperthermia in rat tumors
Authors: Frank Juergen , Lambert Christine , Biesalski Hans Konrad , Thews Oliver , Vaupel Peter , Kelleher Debra K. 
Published: January 2004

AbstractOxidative stress‐related changes in tumors upon localized hyperthermia (HT), 5‐aminolevulinic acid‐based photodynamic therapy (ALA‐PDT) and their combination (ALA+HT) were examined after the observation that the antitumor effects of ALA‐PDT could be significantly enhanced upon simultaneous application of HT. Rats bearing s.c. DS‐sarcomas (0.6–1.0 ml) on the hind foot dorsum were anesthetized and underwent one of the following treatments: (i) ALA‐PDT (375 mg/kg 5‐ALA i.v.); (ii) localized HT, 43°C for 60 min; (iii) combined ALA‐PDT and HT [=ALA+HT]. Appropriate control experiments were also performed. After treatment, tumors were excised and rapidly frozen for later analysis of nitrosative stress (protein nitration), apoptotic events (TUNEL, caspase activation, DNA and RNA fragmentation), expression of heat shock proteins (hsp70 and HO‐1), glutathione (GSH) levels and glutathione peroxidase (GPx) activity. Protein nitration was found to increase upon treatment, being especially pronounced in the ALA+HT group, and could partially be related to areas surrounding microvessels. The extent of nitrosative stress also correlated well with the appearance of the markers of apoptosis and the inhibition of in vivo tumor growth as seen in a previous study. GSH levels decreased upon treatment, the reduction being most prominent in the ALA‐PDT and ALA+HT groups. GPx activity, however, showed a significant decrease only in the ALA‐PDT group. Whereas hsp70 expression increased upon HT, ALA‐PDT caused a decrease, and these opposing effects were nullified with ALA+HT. The results obtained point to a number of cellular mechanisms—including effects on cellular defense mechanisms and an abrogation of the heat shock defense mechanism—that may interact to achieve the potentiated tumor response rate seen in vivo upon combined treatment. © 2003 Wiley‐Liss, Inc.
DNA methylation of RASSF1A, HIN‐1, RAR‐β, Cyclin D2 and Twist in in situ and invasive lobular breast carcinoma
Authors: Fackler Mary Jo , McVeigh Megan , Evron Ella , Garrett Elizabeth , Mehrotra Jyoti , Polyak Kornelia , Sukumar Saraswati , Argani Pedram 
Published: January 2004

AbstractLittle is known about epigenetic silencing of genes by promoter hypermethylation in lobular breast cancers. The promoter methylation status of 5 cancer‐related genes (RASSF1A, HIN‐1, RAR‐β, Cyclin D2 and Twist) was evaluated in 2 types of lobular cancers, in situ (LCIS) and invasive lobular carcinomas (ILC) (n = 32), and compared to ductal in situ (DCIS) and invasive (IDC) breast cancers (n = 71). By using methylation‐specific PCR (MSP), 100% of ILC and 69% of LCIS cases were found to have 1 or more hypermethylated genes among the panel of 5 genes (compared to 100% IDC and 95% of DCIS). Two or more hypermethylated genes were detected per tumor in 79% of invasive and 61% of in situ lobular carcinomas compared to 81% of IDC and 77% of DCIS. By contrast, DNA from nearly all normal reduction mammoplasty tissues (n = 8) was unmethylated for the 5 genes. The methylation profiles of lobular vs. ductal carcinomas with respect to RASSF1A, Cyclin D2, RARβ, and Hin‐1 genes were similar, suggesting that gene silencing by promoter hypermethylation is likely to be important in both groups of diseases. Distinctly different, Twist was hyper‐ methylated less often in ILC (16%, 3/19 cases) than in IDC (56%, 15/27 cases) (p = 0.01). These results suggest that these 2 types of tumors share many common methylation patterns and some molecular differences. Additional studies might lend further understanding into the etiology and clinical behavior of this tumor type. © 2003 Wiley‐Liss, Inc.
DNA adduct formation by the anticancer drug ellipticine in rats determined by 32P postlabeling
Authors: Stiborová Marie , Breuer Andrea , Aimová Dagmar , Stiborová‐Rupertová Martina , Wiessler Manfred , Frei Eva 
Published: January 2004

AbstractEllipticine is a potent antineoplastic agent whose mode of action is considered to be based mainly on DNA intercalation and/or inhibition of topoisomerase II. Recently, we found that ellipticine also forms covalent DNA adducts in vitro and that the formation of the major adduct is dependent on the activation of ellipticine by cytochrome P450 (CYP). Here, we investigated the capacity of ellipticine to form DNA adducts in vivo. Male Wistar rats were treated with ellipticine, and DNA from various organs was analyzed by 32P postlabeling. Ellipticine‐specific DNA adduct patterns, similar to those found in vitro, were detected in most test organs. Only DNA of testes was free of the ellipticine‐DNA adducts. The highest level of DNA adducts was found in liver (19.7 adducts per 107 nucleotides), followed by spleen, lung, kidney, heart and brain. One major and one minor ellipticine‐DNA adducts were found in DNA of all these organs of rats exposed to ellipticine. Besides these, 2 or 3 additional adducts were detected in DNA of liver, kidney, lung and heart. The predominant adduct formed in rat tissues in vivo was identical to the deoxyguanosine adduct generated in DNA by ellipticine in vitro as shown by cochromatography in 2 independent systems. Correlation studies showed that the formation of this major DNA adduct in vivo is mediated by CYP3A1‐ and CYP1A‐dependent reactions. The results presented here are the first report showing the formation of CYP‐mediated covalent DNA adducts by ellipticine in vivo and confirm the formation of covalent DNA adducts as a new mode of ellipticine action. © 2003 Wiley‐Liss, Inc.
Induction of apoptosis and chemosensitization of mesothelioma cells by Bcl‐2 and Bcl‐xL antisense treatment
Authors: Hopkins‐Donaldson S , Cathomas R , Simões‐Wüst AP , Kurtz S , Belyanskya L , Stahel RA , Zangemeister‐Wittke U 
Published: January 2004

AbstractThe original article to which this Erratum refers was published in International Journal of Cancer (2003) 106(2) 160–166
Stage at diagnosis is a key explanation of differences in breast cancer survival across Europe
Authors: Sant M , Allemani C , Capocaccia R , Hakulinen T , Aareleid T , Coebergh JW , Coleman MP , Grosclaude P , Martinez C , Bell J , Youngson J , Berrino F 
Published: January 2004

AbstractThe original article to which this Erratum refers was published in International Journal of Cancer (2003) 106(3) 416–422
Cancer occurrence in Ardabil: Results of a population‐based Cancer Registry from Iran
Authors: Sadjadi A , Malekzadeh R , Derakhshan MH , Sepehr A , Nouraie M , Sotoudeh M , Yazdanbod A , Shokoohi B , Mashayekhi A , Arshi S , Majidpour A , Babaei M , Mosavi A , Mohagheghi MMA , Alimohammadian M 
Published: January 2004

AbstractThe original article to which this Erratum refers was published in International Journal of Cancer (2003) 107(1) 113–118
The biological effects of N3‐methyladenine
Authors: Fronza Gilberto , Gold Barry 
Published: January 2004

AbstractThe targeting of damage to DNA remains an attractive strategy to kill tumor cells. One of the serious side effects of alkylating agents is that they create both toxic (desired) and mutagenic (undesired) lesions. The result is that patients successfully treated for a primary cancer are at significant risk to develop cancer related to their therapy. To address this issue we have prepared agents that selectively methylate DNA at the N3‐position of adenine. The presence of this lesion in DNA is thought to halt DNA polymerase, and this then initiates a cascade of events including cell death. The toxicity and mutagenicity of the compound, Me‐lex, used to generate N3‐methyladenine is discussed in bacterial, yeast, and mammalian systems. Mechanisms are proposed to explain the biological activities of N3‐methyladenine. © 2003 Wiley‐Liss, Inc.
Modulation of phosphatidylinositol‐3‐kinase/protein kinase B‐ and mitogen‐activated protein kinase‐pathways by tea polyphenols in human prostate cancer cells
Authors: Siddiqui Imtiaz Ahmad , Adhami Vaqar Mustafa , Afaq Farrukh , Ahmad Nihal , Mukhtar Hasan 
Published: January 2004

AbstractWe have earlier shown that oral infusion of a polyphenolic fraction isolated from green tea, at a human achievable dose (equivalent to six cups of green tea per day), significantly inhibits prostate cancer (PCA) development and metastasis in transgenic adenocarcinoma of mouse prostate (TRAMP) model that closely mimics progressive form of human prostatic disease (Gupta et al. [2001]: Proc. Natl. Acad. Sci. U.S.A. 98:10350–10355.). A complete understanding of the mechanism(s) and molecular targets of PCA chemopreventive effects of tea polyphenols may be useful in developing novel approaches for its prevention. In this study, we employed two distinct human PCA cell lines viz. DU145 (androgen‐unresponsive prostate carcinoma cells) and LNCaP (androgen‐responsive prostate carcinoma cells) and, employing immunoblot analysis, we evaluated the effect of epigallocatechin‐3‐gallate (EGCG), the major polyphenol present in green tea and theaflavins (TF), the major polyphenol present in black tea on phosphatidylinositol‐3‐kinase (PI3K)/protein kinase B (PKB) and mitogen‐activated protein kinase (MAPK) pathways. Both EGCG and TF treatment were found to (i) decrease the levels of PI3K and phospho‐Akt and (ii) increase Erk1/2 in both DU145 and LNCaP cells. Our data showing the inhibition of the constitutive levels of PI3K and the phosphorylation of Akt could be important because the treatment approaches should be aimed at the inhibition of the constitutive levels of PI3K and Akt. Our data also suggest that Erk1/2 could be involved in the anti‐cancer effects of EGCG and TF. Taken together, our study, for the first time demonstrated the modulation of the constitutive activation of PI3K/Akt and Erk1/2 pathways by EGCG as well as TF. We suggest that detailed studies in appropriate tumor model system are needed to establish the relevance of the cell culture work to in vivo models. © 2003 Wiley‐Liss, Inc.
Identification of molecular targets for dietary energy restriction prevention of skin carcinogenesis: An idea cultivated by Edward Bresnick
Authors: Birt Diane F. , Przybyszewski Joe , Wang Weiqun , Stewart Jeanne , Liu Y. 
Published: January 2004

AbstractDietary energy restriction (DER) has long been known to strikingly inhibit carcinogenesis in many animal models. The animal data has been corroborated by recent and ongoing epidemiological studies demonstrating the importance of energy balance, physical exercise and obesity in human cancer. Dr. Edward Bresnick provided key insights into this important area of research and pivotal direction for the author's research while he served as Director of the Eppley Institute for Research in Cancer, Omaha, NE. These insights moved this research toward demonstrating that DER reduced the expression of key protein kinase C isoforms in mouse skin. More recent studies have uncovered downstream events that are inbibited by DER including blockage of tumor promoter activation of Raf‐1, ERK 1,2 and AP‐1 expression. Parallel studies have demonstrated the DER inhibition of these key cellular signaling events in mouse skin carcinogenesis are dependent upon an intact adrenal gland because adrenalectomized mice fed DER diet did not have reduced tumor burden or inhibited signaling and blocked AP‐1 activation as was observed in DER mice with intact adrenal glands. In addition, the DER inhibition of tumorigenesis and AP‐1 signaling was restored in adrenalectomized mice that were given corticosterone in the drinking water. This showed that in mice in the chemical carcinogenesis protocol glucocorticoid hormone plays a major role in mediating DER prevention of cancer. Studies are ongoing to further assess the mechanism of DER modulation of skin cancer by assessing impacts on transcriptional regulation and expression of genes that are critical in skin carcinogenesis. © 2003 Wiley‐Liss, Inc.
Transcriptional regulation of TNF family receptors and Bcl‐2 family by chemotherapeutic agents in murine CT26 cells
Authors: Choi Kyoung‐Han , Choi Hye Young , Ko Jae‐Kyun , Park Sung‐Shin , Kim Yong‐Nyun , Kim Chul‐Woo 
Published: January 2004

AbstractVarious chemotherapeutic agents have been shown to sensitize cancer cells to members of the tumor necrosis factor (TNF) family. However, it is unclear whether sensitization by chemotherapeutic agents involves the transcriptional regulation of apoptosis‐related genes. In this study, we investigated mRNA regulation of TNF family receptors and Bcl‐2 family members after treating the murine colon cancer cell line, CT26, with various apoptosis inducers. We found that treatment with cycloheximide, a protein synthesis inhibitor, remarkably increased CD40 mRNA levels by semi‐quantitative RT‐PCR. Other protein synthesis inhibitors, such as anisomycin and emetine, also enhanced CD40 mRNA expression, which was significantly blocked by a NF‐κB antagonist and a p38 MAP kinase antagonist. After treatment with cycloheximide, and further cultivation in fresh medium, CD40 protein levels were found to increase by flow cytometry. Additionally, we found that cycloheximide treatment appeared to downregulate the Bcl‐xL mRNA level but not the Bax mRNA level by RNase protection assay. Because the upregulation of CD40 mRNA and the downregulation of Bcl‐xL correlated with CT26 cell death, our results suggest that chemotherapeutic agents, including cycloheximide, may exert their synergistic effects on the TNF family treatment of cancer cells by regulating the mRNA levels of apoptosis‐related genes. © 2003 Wiley‐Liss, Inc.
Hyperplasia, partial hepatectomy, and the carcinogenicity of aflatoxin B1
Authors: Roebuck B.D. 
Published: January 2004

AbstractGeneralized cellular hyperplasia has long been associated as a factor in the causation of liver cancer. Parenchymal cell hyperplasia resulting from hepatotoxins, viruses, parasites, or malnutrition is exceedingly variable as to when it occurs, its extent, and its duration. Partial hepatectomy has been used as an experimental tool precisely because the timing and extent of hyperplasia can be known and controlled. With regards to aflatoxin B1 (AFB1) carcinogenesis, partial hepatectomy has produced variable results. An explanation appears to reside in the hepatotoxic properties of AFB1 that enhance the early stages of carcinogenesis. © 2003 Wiley‐Liss, Inc.
Tailoring cancer chemoprevention regimens to the individual
Authors: Conney Allan H. 
Published: January 2004

AbstractThe present article, which is a tribute to the memory of Dr. Edward Bresnick, emphasizes the importance of environmental and life‐style factors for cancer causation in the human population and points out approaches to cancer prevention. These approaches include vaccinations for the prevention of cancers that are caused by infectious agents as well as the use of cancer chemopreventive agents. The use of tamoxifen and letrozole to prevent breast cancer, finasteride to prevent prostate cancer, sunscreens or topical applications of 5‐fluorouracil to prevent sunlight‐induced skin cancer, and aspirin or calcium to prevent colon cancer are a few examples of cancer chemoprevention in high risk individuals and in the general population. An underdeveloped area of cancer chemoprevention is the use of combinations of agents that work by different mechanisms. It was pointed out that animal studies indicate that many cancer chemopreventive agents inhibit carcinogenesis under one set of experimental conditions but enhance carcinogenesis under another set of experimental conditions. These observations suggest that tailoring the chemopreventive regimen to the individual or to groups of individuals living under different environmental conditions or with different mechanisms of carcinogenesis may be an important aspect of cancer chemoprevention in human populations. How to tailor cancer chemoprevention regimens to the individual is an important challenge for the future. © 2003 Wiley‐Liss, Inc.
Molecular integrals over the gauge‐including atomic orbitals. II. The Breit–Pauli interaction
Authors: Ishida Kazuhiro 
Published: January 2004

AbstractEach accompanying coordinate expansion (ACE) formula is derived for each of the orbit–orbit interaction, the spin–orbit coupling, the spin–spin coupling, and the contact interaction integrals over the gauge‐including atomic orbitals (GIAOs) by the use of the solid harmonic gradient (SHG) operator. Each ACE formula is the general formula derived at the first time for each of the above molecular integrals over GIAOs. These molecular integrals are arising in the Breit–Pauli two‐electron interaction for a relativistic calculation. We may conclude that we can derive a certain ACE formula for any kind of molecular integral over solid harmonic Gaussian‐type orbitals by using the SHG operator. The present ACE formulas will be useful, for example, for a calculation of a molecule in a uniform magnetic field, for a relativistic calculation, and so on, with the GIAO as a basis function. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 1874–1890, 2003