bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ewing tumours and synovial sarcomas have critical features of karyotype evolution in common with epithelial tumours
Authors: Höglund Mattias , Gisselsson David , Mandahl Nils , Mitelman Felix 
Published: March 2005

AbstractWe have analysed the accumulated cytogenetic data on karyotypic evolution in Ewing tumours (ET) and synovial sarcomas (SS). Both tumour types frequently show balanced translocations, t(11;22) and t(X;18), respectively, that result in specific fusion genes. The analyses revealed +8, +12, +1q, and 16q− as important secondary changes to t(11;22) in ET and the imbalances showed a distinct temporal order. By principal component analysis, one major karyotypic pathway dominated by gains and one minor dominated by losses were identified. The kartyotypic evolution pattern in SS was less distinct. Both ET and SS showed a power law distribution of the number of acquired aberrations, which in both tumour types conformed to a distribution with an exponent equal to 1. Similar distributions are frequently found in epithelial tumours. ET and SS differ in this respect from other malignancies with balanced translocations resulting in fusion genes, which typically show a power law distribution of the number of acquired aberrations with exponents close to 2. This suggests that chromosome changes in ET and SS may develop through mechanisms more similar to those in epithelial tumours lacking recurrent balanced rearrangements than in haematological malignancies characterised by balanced translocations leading to fusion genes. © 2005 Wiley‐Liss, Inc.
Phenotypic persistence after reoxygenation of hypoxic neuroblastoma cells
Authors: Holmquist Linda , Jögi Annika , Påhlman Sven 
Published: March 2005

AbstractFast‐growing solid tumors are usually insufficiently vascularized, leading to areas with necrosis and/or poorly oxygenated cells. Tumor cells adapt to acute hypoxic stress. Central to this adaptation are the hypoxia‐inducible transcription factors (HIFs), which are degraded at normoxic but become stabilized at hypoxic conditions. Hypoxic (1% O2) neuroblastoma cells downregulate sympathetic nervous system marker genes, whereas neural crest cell markers are upregulated, suggesting that hypoxic tumor cells adopt a less mature phenotype, which in the clinical setting would translate to more aggressive tumors with increased metastatic potential. Here, we compared gene expression patterns in neuroblastoma cells grown at 1%, 5% (a physiologic oxygen level) and 21% O2. At 5% O2, cells developed a weak hypoxic phenotype and HIF‐2 α, but not HIF‐1 α, was acutely stabilized. At 1% O2, HIF‐2 α protein remained present in long‐term cultures, while HIF‐1 α was present only transiently. The stability of the hypoxia‐induced dedifferentiated phenotype in cells acutely reoxygenated at either 21% or 5% O2 persisted for at least 24 hr. Genes associated with a differentiated state, like NPY, ChrA and ChrB, were still downregulated and hypoxia‐induced genes, like TH and Id2, remained upregulated. Thus, if these culture conditions are viewed as models for acute reoxygenation of metastasizing hypoxic tumor cells, our data suggest that an aggressive hypoxic phenotype persists for 24 hr or more, which might be long enough for the cells to be able to home to secondary sites, in part as a consequence of their immature hypoxic characteristics. © 2005 Wiley‐Liss, Inc.
In vivo and in vitro antitumor activity of butyroyloxymethyl‐diethyl phosphate (AN‐7), a histone deacetylase inhibitor, in human prostate cancer
Authors: Rephaeli Ada , Blank‐Porat Diana , Tarasenko Nataly , Entin‐Meer Michal , Levovich Inesa , Cutts Suzanne M. , Phillips Don R. , Malik Zvi , Nudelman Abraham 
Published: March 2005

AbstractAN‐7, a prodrug of butyric acid, induced histone hyperacetylation and differentiation and inhibited proliferation of human prostate 22Rv1 cancer cells in vitro and in vivo. In nude mice implanted with these cells, 50 mg/kg AN‐7 given orally thrice a week led to inhibition of tumor growth and metastasis, tumor regression in >25% of animals and increased survival. Median time to the experimental end point (tumor volume 2 cm3 or death) in the untreated was 52 days, and average tumor volume was 0.8 ± 0.18 cm3. At the same time, 94.4% of AN‐7‐treated mice survived and had average tumor volumes of 0.37 ± 0.1 cm3. PSA expression was a useful marker for 22Rv1 lung metastasis detection. Sizeable metastases positively stained for PSA and limited air gaps were found in lungs of untreated mice. In animals treated with AN‐7, lung morphology appeared normal. Primary tumors of treated animals were highly positive for PSA and had an elevated level of p21 and the proapoptotic protein Bax. Sections taken from AN‐7‐treated animals, examined under an electron microscope, exhibited condensed chromatin and apoptotic bodies. PSA serum levels were higher in untreated compared to treated animals and correlated with tumor volume. Since prolonged oral administration with 50 mg/kg or a single oral dose of 1.2 g/kg AN‐7 did not cause adverse effects and the former exhibited significant anticancer activity, AN‐7 is likely to display a high therapeutic index and may be beneficial for prostate cancer patients. © 2005 Wiley‐Liss, Inc.
Expression patterns of mitotic and meiotic cell cycle regulators in testicular cancer and development
Authors: Diederichs Sven , Bäumer Nicole , Schultz Nikolaus , Hamra F. Kent , Schrader Mark G. , Sandstede Marie‐Luise , Berdel Wolfgang E. , Serve Hubert , Müller‐Tidow Carsten 
Published: March 2005

AbstractMitotic and meiotic cell cycle regulation is essential for normal development and tumor prevention. The underlying molecular mechanisms are not completely characterized. The aim of our analysis was to derive a global expression map of cell cycle regulators in mitosis and meiosis. First, the expression of cyclins, CDKs and CDK inhibitors was determined during postnatal testis maturation in mice using microarrays and quantitative RT‐PCR. The abundance of cyclins A1, B2, K, M4, CDK2, all CDKLs, CDKN2c, CDKN2d and INCA1 increased during testis maturation. In contrast, cyclins A2, B1, D2, G1, G2, CDK1, CDK4 and CDK2AP1 showed a maturation‐associated decrease. Gene expression profiles of isolated germ cells and testicular somatic cells confirmed these results. Second, we determined cyclin expression patterns in human normal and malignant testis samples (n = 36) modeling the reciprocal difference between meiosis and mitosis. Testicular tumors strictly expressed cell cycle regulators identified in mitotically dividing germ cells. Expression of several transcripts was histology‐specific in testicular tumors, providing novel molecular markers and potential therapeutic targets. Taken together, our data provide a comprehensive expression map of cell cycle regulators at the switch between mitosis and meiosis in testis development and in cancerogenesis. © 2005 Wiley‐Liss, Inc.
Parathyroid hormone–related protein (PTHrP) as a causative factor of cancer‐associated wasting: Possible involvement of PTHrP in the repression of locomotor activity in rats bearing human tumor xenografts
Authors: Onuma Etsuro , Tsunenari Toshiaki , Saito Hidemi , Sato Koh , Yamada‐Okabe Hisafumi , Ogata Etsuro 
Published: March 2005

AbstractNude rats bearing the LC‐6‐JCK human lung cancer xenograft displayed cancer‐associated wasting syndrome in addition to humoral hypercalcemia of malignancy. In these rats, not only PTHrP but also several other human proinflammatory cytokines, such as IL‐6, leukemia‐inducing factor, IL‐8, IL‐5 and IL‐11, were secreted to the bloodstream. Proinflammatory cytokines induce acute‐phase reactions, as evidenced by a decrease of serum albumin and an increase in α1‐acid glycoprotein. Tumor resection abolished the production of proinflammatory cytokines and improved acute‐phase reactions, whereas anti‐PTHrP antibody affected neither proinflammatory cytokine production nor acute‐phase reactions. Nevertheless, tumor resection and administration of anti‐PTHrP antibody similarly and markedly attenuated not only hypercalcemia but also loss of fat, muscle and body weight. Body weight gain by anti‐PTHrP antibody was associated with increased food consumption; increased body weight from anti‐PTHrP antibody was observed when animals were freely fed but not when they were given the same feeding as those that received only vehicle. Furthermore, nude rats bearing LC‐6‐JCK showed reduced locomotor activity, less eating and drinking and low blood phosphorus; and anti‐PTHrP antibody restored them. Although alendronate, a bisphosphonate drug, decreased blood calcium, it affected neither locomotor activity nor serum phosphorus level. These results indicate that PTHrP represses physical activity and energy metabolism independently of hypercalcemia and proinflammatory cytokine actions and that deregulation of such physiologic activities and functions by PTHrP is at least in part involved in PTHrP‐induced wasting syndrome. © 2005 Wiley‐Liss, Inc.
Combined subcarcinogenic benzo[a]pyrene and UVA synergistically caused high tumor incidence and mutations in H‐ras gene, but not p53, in SKH‐1 hairless mouse skin
Authors: Wang Yongyin , Gao Dayuan , Atencio David P. , Perez Evangeline , Saladi Rao , Moore Julian , Guevara Denise , Rosenstein Barry S. , Lebwohl Mark , Wei Huachen 
Published: March 2005

AbstractCombined subcarcinogenic doses of benzo[a]pyrene (BaP) and UVA induced H‐ras, but not p53, gene mutations 8 weeks before tumor emergence in SKH‐1 mice. Neither UVA (40 kJ/m2) nor BaP (8 nmol) induced any tumors after mice were topically treated 3 times/week for 25 weeks. However, combined BaP‐UVA treatment synergistically increased tumor incidence and multiplicity. All tumors induced by BaP‐UVA were malignant. The epidermis was collected from mice treated for 2, 6 and 10 weeks. DNA from UVB‐ (0.3 kJ/m2) or BaP‐UVA‐(8 nmol and 40 kJ/m2‐induced tumors was isolated and screened for H‐ras and p53 mutations. Four types of point mutation, GGC→GAC, GCC, GTC and CGC, occurred in UVB‐induced tumors at H‐ras codon 13; and one type of point mutation, GGA→GAA, at codon 12. Treatment with either BaP alone or BaP‐UVA for 10 weeks caused GGA→GAA mutation at codon 12 or GGC→GAC mutation at codon 13 in nontumor skin, respectively, as well as in tumors induced by BaP‐UVA. All of the 10‐week samples treated with either BaP or BaP‐UVA showed detectable mutations at codons 12 and 13, but the genetic load was significantly higher in BaP‐UVA‐treated mice than in those exposed only to BaP. UVA alone induced mutations at codon 12 in only one‐third of samples. G→A mutations induced by BaP or BaP‐UVA at position 38 of codon 13 have not been reported previously. C→T transitions were detected in p53 hot spots of exon 8 in 2 of 19 BaP‐UVA‐induced tumors but were not found in nontumor skin. © 2005 Wiley‐Liss, Inc.
CDC91L1 (PIG‐U) mRNA expression in urothelial cell carcinomas
Authors: Schultz Iman J. , Kiemeney Lambertus A. , Witjes J. Alfred , Schalken Jack A. , Willems Johannes L. , Swinkels Dorine W. , de Kok Jacques B. 
Published: March 2005

AbstractCDC91L1 (PIG‐U) was recently discovered as a new oncogene in human bladder cancer and showed mRNA overexpression in 36% of primary bladder tumor tissues compared to normal urothelium. We further investigated CDC91L1 mRNA expression in 8 bladder cancer cell lines, 14 normal bladder tissues and 42 urothelial cell carcinomas by real‐time quantitative PCR. The prognostic value of CDC91L1 mRNA expression was also investigated. Surprisingly, only one (2.4%) tumor tissue showed overexpression compared to normal urothelium. No significant relationship of CDC91L1 mRNA expression with increasing pathologic stage (p = 0.962) or grade (p = 0.557) was observed. Median normalized CDC91L1 mRNA expression values were 0.19 for superficial tumors (n = 21) and 0.18 for invasive tumors (n = 21). Grade I, grade II and grade III tumors had median normalized expression values of 0.26, 0.18 and 0.33, respectively. CDC91L1 mRNA expression level was not indicative of early tumor recurrence (log rank p = 0.1629), tumor progression (log rank p = 0.9307) or overall and disease‐specific survival (log rank p = 0.9193 and 0.4710, respectively). Our results suggest, in contrast to those of Guo et al. (Nat Med 2004;10:374–81), that the oncogene CDC91L1 is not overexpressed at the mRNA level in urothelial cell carcinomas and cannot be used to predict the course of the disease. © 2005 Wiley‐Liss, Inc.
CYP19 (aromatase) haplotypes and endometrial cancer risk
Authors: Paynter Randi A. , Hankinson Susan E. , Colditz Graham A. , Kraft Peter , Hunter David J. , De Vivo Immaculata 
Published: March 2005

AbstractEndogenous estrogen exposure is an important determinant of endometrial cancer risk. Aromatase, encoded by CYP19, catalyzes the aromatization of androstenedione and testosterone to estrone and estradiol, respectively. Several common genetic polymorphisms in CYP19 have been identified, including a TCT insertion/deletion and a (TTTA)n repeat polymorphism in intron IV as well as a 3′UTR C/T polymorphism. We evaluated these 3 polymorphisms plus an additional 9 noncoding polymorphisms as individual genotypes and predicted haplotypes as risk factors for endometrial cancer using a nested case‐control study design. Invasive endometrial cancer cases (n = 222) and matched controls (n = 666) were identified among participants in the Nurses' Health Study who had provided a blood sample in 1989–1990 (n = 32,826). We estimated haplotypes from unphased genotype data spanning >123 kb of CYP19. Six haplotypes constructed from 10 SNPs were estimated with a frequency ≥5%. The highest prevalence haplotype (33% among cases, 28% among controls) was significantly associated with endometrial cancer risk (p = 0.03). Loci with variant alleles that comprise the risk haplotype were independently associated with endometrial cancer, with relative risk estimates ranging from 1.68 (95% CI 1.13–2.48) to 2.07 (95% CI 1.33–3.23), comparing variant allele carriers to wild‐type homozygotes. We observed significant interactions between menopausal status and 2 of the high‐risk loci (p = 0.03 and p < 0.01), with >2‐fold increased risk for variant allele carriers who were postmenopausal but no association between genotype and endometrial cancer among premenopausal women. We evaluated associations between CYP19 haplotypes and plasma steroid hormone levels. The haplotype associated with endometrial cancer risk is also significantly associated with the ratios of estrone to androstenedione and estradiol to testosterone, the products and substrates of the enzyme aromatase, encoded by CYP19. Our data suggest that there is a high‐frequency CYP19 haplotype related to higher estrogen to androgen ratios and increased risk of endometrial cancer and that this association may primarily pertain to postmenopausal women. (Supplementary material for this article can be found on the International Journal of Cancer website at http:www.interscience.wiley.com/jpages/0020‐7136/suppmat/index.html.) © 2005 Wiley‐Liss, Inc.
Sequential, randomized trial of a low‐fat, high‐fiber diet and soy supplementation: Effects on circulating IGF‐I and its binding proteins in premenopausal women
Authors: Gann Peter H. , Kazer Ralph , Chatterton Robert , Gapstur Susan , Thedford Kim , Helenowski Irene , Giovanazzi Sue , Van Horn Linda 
Published: March 2005

AbstractDespite evidence supporting the involvement of the IGF system in the development of breast and other cancers, the major determinants of interindividual variability in circulatory IGF‐I levels are not well understood. Previous research has pointed to important genetic influences as well as dietary effects through marked calorie or protein restriction. We conducted a randomized trial to determine the effects of 2 dietary patterns on serum IGF‐1, IGFBP1 and IGFBP3 in free‐living premenopausal women: phase 1, an isocaloric low‐fat, high‐fiber (LFHF) vs. usual diet, and phase 2, a soy supplement either with or without isoflavones (soy+IF vs. soy–IF). Participants completed 12 menstrual cycles on phase 1 and then were randomly assigned to a soy supplement for 3 cycles while maintaining the phase 1 diet. Before and after each phase, 154 women provided serum. We found no difference in the change in IGF‐I, BP1 or BP3 in the LFHF group compared to the usual diet group. In phase 2, there were no differences in any IGF protein between the soy+IF and the soy–IF groups or any evidence of interaction between isoflavone exposure and the background diet. However, there was a small but statistically significant decrease (2.3%) in BP3 and an increase in the IGF‐I:BP3 molar ratio among all 153 subjects following either soy supplement. These changes were correlated with changes in intake of calcium, total vegetable protein and soy. The results are compatible with previous data suggesting that increases in dietary calcium, protein and soy, in particular, could increase circulating levels of bioavailable IGF‐I. © 2005 Wiley‐Liss, Inc.
Five‐year follow‐up of health‐related quality of life after primary treatment of localized prostate cancer
Authors: Korfage Ida J. , Essink‐Bot Marie‐Louise , Borsboom Gerard J.J.M. , Madalinska Joanna B. , Kirkels Wim J. , Habbema J. Dik F. , Schröder Fritz H. , de Koning Harry J. 
Published: March 2005

AbstractAlthough with earlier detection of prostate cancer more men face the long‐term consequences of primary treatment, studies on the impact of treatment on long‐term health‐related quality of life (HRQoL) are scarce. We followed 314 men with newly diagnosed localized prostate cancer from 1 month before until 5 years after radical prostatectomy (n = 127) or external beam radiotherapy (n = 187; median follow‐up = 52 months). Questionnaires addressing disease‐specific (UCLA PCI) and generic (SF‐36, EQ‐5D) HRQoL were sent 1 month before and 6, 12 and 52 months after treatment. Repeated‐measures modeling was used to study HRQoL over time. Regular urinary leakage was reported by 12% of prostatectomy patients before treatment and by 31% at the 52‐month assessment. Erectile dysfunction before treatment was reported by 31% of prostatectomy patients and by 40% of radiotherapy patients; at the 52‐month assessment, these percentages were 88% and 64%, respectively. Erectile dysfunction present at 1 year posttreatment can be considered permanent. Prostatectomy patients reported better generic functioning both before and after treatment than radiotherapy patients, who were on average 5.9 years older and had more comorbid conditions. General physical functioning of prostatectomy patients slightly improved over time, but declined in radiotherapy patients. The relation between age and physical scores was found to be nonlinear. The long‐term physical decline in radiotherapy patients partly resulted from aging and its nonlinear impact on health, although treatment effects cannot be excluded. Scores of both patient groups remained above those of norm populations. Innovative graphs describing disease‐specific and generic functions after treatment can help patients and physicians in their treatment choices. © 2005 Wiley‐Liss, Inc.
Is there an association between maternal weight and the risk of testicular cancer? An epidemiologic study of Norwegian data with emphasis on World War II
Authors: Aschim Elin L. , Grotmol Tom , Tretli Steinar , Haugen Trine B. 
Published: March 2005

AbstractSince registration started in the 1950s, the incidence of testicular cancer (TC) in the Western world has increased, which is also the case in Norway. Men born in Norway during World War II (WWII), however, have a lower TC incidence than men born in the years before or after WWII. Increased fetal exposure to estrogen during the first trimester of pregnancy has been proposed as a risk factor for the development of TC later in life. Increased maternal weight is associated with higher insulin levels, leading to lower sex hormone‐binding globulin levels and thereby increased levels of bioavailable estrogens for transplacental transfer from mother to fetus. The aim of the present study was therefore to examine whether there was an association between maternal weight and the incidence of TC among those who were born in a time period where the nutritional conditions changed, i.e., around the time of WWII. We compared data for a random sample of women giving birth in Oslo, Norway, in the years 1931 to 1955 with the TC incidence among men born in the whole country in the same time period. Maternal weight at delivery was used as a proxy for first‐trimester weight. We found a correlation (Spearman's rho = 1.00, p < 0.01; Pearson's r = 0.95, p = 0.02) between the TC incidence and maternal weight adjusted for birth weight and maternal age. Although one cannot draw firm conclusions from ecologic correlations, these findings suggest that the increase in TC incidence over the past decades could be at least partly attributed to the increased maternal body weight observed in most populations in the relevant time period since TC is thought to be associated with in utero conditions. © 2005 Wiley‐Liss, Inc.
Dendritic cells delivered inside human carcinomas are sequestered by interleukin‐8
Authors: Feijoó Esperanza , Alfaro Carlos , Mazzolini Guillermo , Serra Patricia , Peñuelas Iván , Arina Ainhoa , Huarte Eduardo , Tirapu Iñigo , Palencia Belén , Murillo Oihana , Ruiz Juan , Sangro Bruno , Richter José A. , Prieto Jesús , Melero Ignacio 
Published: March 2005

AbstractIn the course of a clinical trial consisting of intratumoral injections of dendritic cells (DCs) transfected to produce interleukin‐12, the use of 111In‐labeled tracing doses of DCs showed that most DCs remained inside tumor tissue, instead of migrating out. In search for factors that could explain this retention, it was found that tumors from patients suffering hepatocellular carcinoma, colorectal or pancreatic cancer were producing IL‐8 and that this chemokine attracted monocyte‐derived dendritic cells that uniformly express both IL‐8 receptors CXCR1 and CXCR2. Accordingly, neutralizing antihuman IL‐8 monoclonal antibodies blocked the chemotactic attraction of DCs by recombinant IL‐8, as well as by the serum of the patients or culture supernatants of human colorectal carcinomas. In addition, tissue culture supernatants of colon carcinoma cells inhibited DC migration induced by MIP‐3β in an IL‐8‐dependent fashion. IL‐8 production in malignant tissue and the responsiveness of DCs to IL‐8 are a likely explanation of the clinical images, which suggest retention of DCs inside human malignant lesions. Impairment of DC migration toward lymphoid tissue could be involved in cancer immune evasion. © 2005 Wiley‐Liss, Inc.