bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of effects of growth factors and protein kinase C activators on cellular sensitivity to cis‐diamminedichloroplatinum(II)
Authors: Basu Alakananda , Evans Rhobert W. 
Published: February 2007

AbstractThe anti‐proliferative activity of the DNA‐interactive anti‐cancer agent cis‐diamminedichloroplatinum(11) (cDDP) can be modulated by intracellular signaling systems. We have investigated the effects of growth factors on the sensitivity of human cervical carcinoma (HeLa) cells to cDDP. A 24‐hr pretreatment of HeLa cells with 10 ng/ml epidermal growth factor (EGF) or transforming growth factor‐α increased the anti‐proliferatfve activity of cDDP by 2‐ to 4‐fold. A similar pretreatment of HeLa cells with EGF did not alter cellular sensitivity to doxorubicin or vincristine. A brief exposure (15 min) to growth factors was not sufficient for cDDP sensitization. EGF caused a modest and transient increase in cellular diacylglycerol, the endogenous activator of protein kinase C. Bryostatin I, a partial agonist of protein kinase C, antagonized phorbol ester‐mediated cDDP sensitization but had no effect on EGF‐mediated sensitization to cODP. Both EGF and phorbol 12,13‐dibutyrate (PDBu) enhanced the rate of [195mPt]cDDP uptake but had no effect on the rate of [195mPt]cDDP efflux in HeLa cells. Bryostatin I reversed the increase in [195mPt]cDDP content by PDBu but failed to block EGF‐induced increase in [195mPt]cDDP accumulation. Therefore, although the mechanism of tDDP sensitization by both EGF and phorbol ester appears to involve enhanced drug uptake, they may utilize distinct signal transduction pathways.
Dietary fat, olive oil intake and breast cancer risk
Authors: Martin‐Moreno Jose M. , Willett Walter C. , Gorgojo Lydia , Banegas Jose R. , Rodriguez‐Artalejo Fernando , Fernandez‐Rodriguez Juan C. , Maisonneuve Patrick , Boyle Peter 
Published: February 2007

AbstractAs part of a population‐based case‐control study on diet and breast cancer in Spain, the role of dietary fat and vegetable oils in breast cancer etiology was examined. A validated, semi‐quantitative food‐frequency questionnaire was completed by 762 women, 18‐75 years of age, with histologically confirmed, newly diagnosed breast cancer, and 988 randomly selected female controls. For each food item and nutrient, the study subjects were divided into quartiles according to intake levels, with the lowest quartile serving as the reference category. Adjustment for total energy intake and other potential confound‐ers was made using multiple logistic regression for all women as well as separately for pre‐ and post‐menopausal women. Neither total fat intake nor specific types of fat were significantly associated with breast cancer in pre‐ or post‐menopausal women. However, higher consumption of olive oil (rich in monounsaturated fat) was significantly related to a lower risk of breast cancer [for highest vs. lowest quartile of consumption, odds ratio (OR) = 0.66; 95% Cl, 0.46‐0.97] with a significant dose‐response trend. While these findings do not support a relation between total fat intake and breast cancer risk, they do provide evidence for an inverse association between olive oil (and suggest one between monounsaturated fat) and risk of breast cancer.
c‐myc oncogene amplification and cytometric DNA ploidy pattern as prognostic factors in musculoskeletal neoplasms
Authors: Barrios Carlos , Castresana Javier S. , Falkmer Ursula G. , Rosendahl Ingvar , Kreicbergs Andris 
Published: February 2007

AbstractThe relationship between c‐myc oncogene amplification in neoplastic cells as determined by means of Southern‐blot analysis, and their nuclear DNA content as assessed by combined flow and image cytometry, was investigated in fresh tumor specimens from 33 patients with musculoskeletal neoplasms. Amplification, without rearrangement of the c‐myc proto‐oncogene, was detected in 4 out of 7 bone sarcomas and in 6 out of 26 soft‐tissue sarcomas, but in none of 3 benign giant‐cell bone tumors. Among the 10 cases with c‐myc amplification, 2 were found to be cytometrically DNA diptoid, 2 DNA tetraploid, and 6 DNA aneuploid. Conversely, there were 10 tumors displaying extremely aneuploid DNA patterns without c‐myc oneogene amplification. Thus, there was no relationship between c‐myc amplification and DNA ploidy; neither did the percentage of S‐phase cells, as determined by means of image cytometry, correlate significantly with the occurrence of c‐myc amplification. A surprising sex‐bias was observed; all 6 cases of c‐myc‐amplified soft‐tissue sarcomas occurred in females, whereas none of the 11 males with such sarcomas showed this amplification. When the clinical follow‐up data of the patients were scrutinized, it was found that the DNA ploidy pattern of the neoplastic cell nuclei, in combination with the S‐phase values, as well as the occurrence of c‐myc amplification, yielded prognostic information, being statistically significant 2 years after the diagnosis.
PCR‐RFLP studies on chromosome 3p in formaldehyde‐fixed, paraffin‐embedded cervical cancer tissues
Authors: Karlsen Frank , Rabbitts Pamela H. , Sundresan Vasi , Hagmar Bjørn 
Published: February 2007

AbstractLoss of heterozygosity (LOH) has been extensively studied on the short arm of chromosome 3, and functional proofs have been obtained defining a tumor‐suppressor locus at 3p21‐22. We examined 31 paraffin‐embedded cervical cancer samples for LOH, using 5 PCR‐primer pairs, located around 3p21. Allele loss was found in 19 out of the 27 informative samples (70%) while 13 out of 23 informative samples (56%) had LOH located at 3p2l‐22. More of the human papillomavirus (HPV)‐positive samples had LOH compared to the HPV‐negative samples, giving only a weak association between loss of allele and HPV integration. Modifications of the DNA in the formaldehyde‐fixed samples were detected, and further studies will be required to clarify how such artifacts may affect restriction fragment length polymorphism (RFLP) studies on fixed tissues.
Role of clinical criteria in the diagnosis of hereditary non‐polyposis colorectal cancer (HNPCC): Results of a multivariate analysis
Authors: Percesepe Antonio , Anti Marcello , Marra Giancarlo , Roncucci Luca , Pahor Marco , Ccco Claudio , Armelao Franco , Gasbarrini Giovanni , De Leon Maurizio Ponz 
Published: February 2007

AbstractHereditary non‐polyposis colorectal cancer (HNPCC) is an autosomal dominant disease characterized by early‐onset colorectal tumors, primarily in the right colon, that are frequently associated with other cancers. In the absence of a reliable biomarker, clinical criteria for diagnosing HNPCC have been proposed by the International Collaborative Group on HNPCC (ICG‐HNPCC). However, these criteria are often too restrictive for application in small families. We analyzed 6 clinical/ pathological features suggestive of genetic colon‐cancer risk in 970 colorectal‐cancer patients defined according to the ICG criteria as HNPCC (96) or non‐HNPCC (874). Logistic regression analysis was used to determine their relative potentials for predicting the diagnosis of HNPCC. The most predictive were then used to estimate HNPCC risk levels within the non‐HNPCC group. Multivariate analysis showed the following associations with HNPCC diagnosis: vertically transmitted cancer (“highly predictive”), eariy‐onset (<50 yrs) colorectal cancer, aggregation of tumors in the nuclear pedigree and proximal‐colon tumors (the last 3 considered “predictive”). Re‐evaluation of all families revealed that 76 non‐HNPCC families (8.9% of the whole series) satisfied our highly predictive vertical‐transmission criterion plus at least one of the other “predictive” criteria. The presence of 2 consecutive generations affected by colorectal cancer or early primaries seems to be a major risk indicator of hereditary colorectal cancer. Using this approach we identified a large group of families that require further evaluation, although they do not currently meet the ICG‐HNPCC criteria for HNPCC.
Loss of heterozygosity at the RB locus correlates with loss of RB protein in primary malignant neuro‐endocrine lung carcinomas
Authors: Gouyer Valérie , Gazzeri Sylvie , Brambilla Elisabeth , Bolon Isabelle , Moro Denis , Perron Pascal , Benabid Alim Louis , Brambilla Christian 
Published: February 2007

AbstractRB protein expression and loss of heterozygosity (LOH) in the RB gene were studied in 77 primary lung carcinomas of all histological types. RB protein expression was studied by immunohistochemistry with 3 anti‐RB antibodies, and was found altered in 23/29 (79%) neuro‐endocrine (NE) carcinomas and in 18/48 (37%) non‐NE carcinomas. RB gene allele status was studied with 3 probes detecting RFLP in RB locus. Fifty‐five patients were informative, and loss of heterozygosity was detected in 29 (52%) of the corresponding tumors with 1 of the 3 probes used; 89% of the informative NE carcinomas, excluding careinoids, and only 13% of the non‐NE carcinomas exhibited LOH and loss of RB‐protein expression. LOH at the RB locus was strongly correlated with the absence of RB protein in malignant NE carcinomas, and this association was strongly correlated with the neuro‐endocrine phenotype. Inactivation of the RB protein in primary NE carcinomas, excluding carcinoids, therefore seems to imply in the majority of cases the mutation of one allele and loss of the remaining allele of the Rfl gene, leading to loss of RB‐protein expression. In contrast, RB‐protein expression was independent of allele status in non‐NE carcinomas and carcinoids.
Formation of 8‐hydroxy‐2′‐deoxyguanosine and 4‐hydroxy‐2‐nonenal‐modified proteins in human renal‐cell carcinoma
Authors: Okamoto Keisei , Toyokuni Shinya , Uchida Koji , Ogawa Osamu , Takenewa Jun , Kakehi Ynshiyuki , Kinoshita Hidefumi , Hattori‐Nakakuki Yukari , Hiai Hiroshi , Yoshida Osamu 
Published: February 2007

AbstractTo study the possible involvement of reactive oxygen species (ROS) in the tumor biology of human renal‐cell carcinoma (RCC), we analvzed 35 cases of RCC for 2 parameters of oxidative damage: 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), a mutation‐prone DNA‐ base ‐modified product, was measured by means of high‐performance liquid chromatography (HPLC) with an electrochemical (EC) detector, and 4‐hydroxy‐2‐nonenal (HNE)‐modified proteins were measured with a poly‐clonal antibody against HNE‐modified proteins. A 54% higher content of 8‐OHdG was found in RCC than in the corresponding non‐tumorous kidney, suggesting that the DNA of RCC is more exposed to ROS than is the DNA of non‐tumorous kidneys. Immunohistochemistry for HNE‐modified proteins showed a distinct staining pattern of fine to coarse granularity in the cytoplasm of RCC (n = 15), implying that lipid peroxidation products are located in cytoplasmic organelles. These results suggest that RCC constitutionally elaborates more ROS than is produced by the non‐tumorous parts of kidneys. No correlation was found between clinical stage, histology, age or sex and the 2 parameters examined.
Biological heterogeneity of er‐positive breast cancers in the post‐menopausal population
Authors: Romain Sylvie , Chinot Olivier , Guirou Olivier , Soullière Marc , Martin Pierre‐Marie 
Published: February 2007

AbstractIn the natural history of post‐menopausal patients with primary breast cancer, high estrogen receptor levels (ER) have been associated with a poor recurrence‐free survival. The purpose of this study was to investigate whether there are any biological intratumoral characteristics to support this puzzling clinical observation. In a population of 542 post‐menopausal, primary‐breast‐cancer patients, 3 normal distributions fitted into the frequency distribution curve of the logarithmically transformed ER‐EIA values. The biological profiles of the low ER group, and of the intermediate and high ER groups identified in the ER‐positive population were compared. Parameters correlated with ER functional aspect (progesterone receptors and PS2), receptors of epidermal growth factor (EGFR), protease cathepsin D and tumor proliferation (deduced from thymidine kinase activity) were analyzed. As previously reported, the levels of progesterone receptors and PS2 increased significantly from the low to the high ER groups. The highest levels of cathepsin D and thymidine kinase which have been previously related to a poor prognosis in breast cancer were found in the low ER group, but high levels were, surprisingly, also found in the high ER group. This study indicates that the ER‐positive post‐menopausal population is biologically heterogeneous. The high levels of thymidine kinase found in the high ER group suggest that overexpression of ER may be associated with proliferation enhancement, partly explaining the poor spontaneous prognosis related to this subset.
Conditional expression of human TNF‐α: A system for inducible cytotoxicity
Authors: Sparmann Gisela , Walther Wolfgang , Günzburg Walter H. , Uckert Wolfgang , Salmons Brian 
Published: February 2007

AbstractTumor necrosis factor‐α (TNF‐α) is currently being used in clinical trials for cancer treatment, but toxic side effects, due to systemic administration and high doses, are observed. Inducible expression of TNF may permit selective killing of tumour cells in gene therapy protocols without need for prolonged and/or high‐level TNF expression. A conditional TNF expression vector has been constructed in which the coding sequences of human TNF have been placed under the transcriptional control of the glucocorticoid‐regulated murine mammary tumour virus long terminal repeat (MMTV‐LTR). Negligible levels of TNF expression, associated with no phenotypic alterations, are observed in cells transfected with MMTV‐TNF vectors in the absence of glucocorticoid. Expression levels could be stimulated by the addition of the synthetic glucocorticoid dexamethasone. Increasing expression levels of TNF were associated with enhanced cytotoxicity. Our results suggest the potential use of inducible TNF systems for the treatment of tumours in gene therapy protocols.
Altered growth and phenotype in clonal mycN transfectants of the sk‐n‐sh neuroblastoma cell line
Authors: Gross N. , Miescher G. , Beck D. , Favre S. , Beretta C. 
Published: February 2007

AbstractWe have attempted to distinguish in human neuroblastoma between the effects of mycN on differentiation and its potential to promote malignant progression. Others have observed outgrowth of autocrine cells with evidence of an advanced malignant phenotype in mycN‐transfected clonal cell line derived from the single‐copy mycN neuroblastoma, SK‐N‐SH. We have now transfected the parental cell line with the same mycN expression vector and selected 5 clones characterized by unique and stable chromosomal integration sites and variable exogenous copy numbers. mycN gene expression was variable in the different clones and correlated roughly with the copy number of transfected mycN genes. Clones with minimal levels of mycN gene expression had a neuroblastic phenotype and low numbers of surface HLA class‐1 molecules. Clones with high levels of mycN expression had a Schwann/glial‐like phenotype with higher surface HLA class‐1 display without imbalance of expression of specific loci and accelerated growth. Two such clones were capable of anchorage‐independent growth in the absence of serum, and acquired tumorigenic properties. Our results show that exogenous mycN expression can be associated with a differentiation of neuroblastoma cells along the Schwann/glial pathway and can induce accelerated and autonomous growth.
Pleiotropic drug resistance and survival advantage in leukemic cells with diminished apoptotic response
Authors: Frankfurt Oskar S. , Seckinger Daniel , Sugarbaker Everett V. 
Published: February 2007

AbstractCell line R9 generated by continuous exposure of MOLT‐4 cells to adriamycin was cross‐resistant to a variety of unrelated drugs. The following data indicate that diminished apoptotic response was the mechanism of acquired pleiotropic drug resistance: (i) apoptosis was a common mechanism of cell death for agents expressing cross‐resistance; (ii) induction of apoptosis by drugs, medium depletion and serum deprivation was decreased in R9 cells; (iii) DNA degradation in apoptotic cells was lower in resistant lines, probably reflecting, a modification of apoptotic pathway in resistant cells; (iv) inhibition of cell division and DNA synthesis by drugs was similar in sensitive and resistant cells. These data indicated a similar level of initial damage, as typical for resistance based on modified apoptotic response. There was no difference inbcl‐2 protein level between sensitive and resistant cells. Thus acquired pleiotropic resistance and diminished apoptotic response in R9 cells were induced by a bcl‐2‐independent mechanism. Surface T‐cell antigen CD4 was expressed in MOLT‐4 and lost in R9 cells. The role of CD4 down‐regulation in apoptosis‐related drug resistance remains to be explored. The association between acquired pleiotropic drug resistance and increased survival capacity in unfavorable growth conditions indicated that drug‐induced selection of cells with diminished apoptotic response may stimulate neoplastic progression. Alkylating agents induced similar cytotoxicity and only slightly lower apoptosis in R9 cells in comparison with MOLT‐4 cells. Our data show that some drugs may overcome acquired pleiotropic drug resistance based on the modified apoptotic pathway.
Expression of interleukin 2 receptors on human carcinoma cell lines and tumor growth inhibition by interleukin 2
Authors: Yasumura Satoshi , Lin Wen‐Chang , Weidmann Eckhart , Hebda Patricia , Whiteside Theresa L. 
Published: February 2007

AbstractWe have previously shown that human squamous cell carcinomas (SCC) express the interleukin 2 receptor (IL2R)‐α and ‐β chains, and that the ligand, IL2, directly inhibits growth of the tumor in vitro and in vivo in the tumor xenograft‐nude mice model. We now show that the α and β chains of IL2R are expressed on a variety of human carcinoma cell lines and on normal human keratinocytes in early‐stage cultures. While all carcinoma cells in a population expressed IL2R‐α and ‐β proteins, in keratinocytes obtained from different normal donors, variable proportions of cells were positive, as measured by flow cytometry. The carcinoma lines and 2/5 keratinocyte lines studied were also found to contain transcripts for the IL2R‐γ chain detectable by combined reverse transcription‐PCR (RT‐PCR) and hybridization with the specific cDNA probe. Incubation of the gastric (HR) or renal cell carcinoma (RCC) cell lines, but not of other IL2R+ carcinoma cell lines or normal keratinocytes, in the presence of IL2 resulted in dose‐dependent inhibition of tumor cell growth. Monoclonal antibodies (MAbs) specific for IL2R‐β chain completely reversed this growth inhibitory effect of IL2. The ligand, IL2, also down‐regulated surface expression of its own receptor and of intercellular adhesion molecule‐I (ICAM‐I) or class I major histocompatibility complex (MHC) antigens on IL2R+ tumor cells. All carcinoma cells studied incubated in the presence of IL2 exhibited significantly increased sensitivity to growth‐inhibitory effects of other cytokines such as interferon (IFN)‐γ, tumor necrosis factor (TNF)‐α or transforming growth factor (TGF)‐β. IL2 inhibited growth of the HR cells by arresting a significant proportion of tumor cells in the Go/G1 phase of the cell cycle. Thus, IL2 can have direct effects on IL2R+ carcinoma cells, leading to changes in growth or to increases in sensitivity of tumor cells to cytostatic activities of other cytokines.
Correlation of cellular differentiation in human colorectal carcinoma and adenoma cell lines with metabolite profiles determined by 1H magnetic resonance spectroscopy
Authors: MaCkinnon Wanda B. , Huschtscha Lily , Dent Kathy , Hancock Rebecca , Paraskeva Christos , Mountford Carolyn E. 
Published: February 2007

AbstractThe aim was to determine whether proton magnetic resonance spectroscopy (MRS) could grade human colorectal cells of differing malignant potential. A cell model of tumour development and progression comprising 2 non‐tumorigenic adenoma lines and 4 carcinoma lines of increasing tumorigenicity was chosen. A gradual reduction in cellular differentiation and an accumulation of genetic alterations from adenoma to carcinoma characterized the selected cell lines. One‐dimensional and 2‐dimensional MRS showed that reduced differentiation in the cell model correlated with an increase in the levels of lipid, metabolites, the glycosylation intermediate uridine diphospho‐N‐acetylglucosamine and cell‐surface fucosylation. Mutations involving the K‐ras, APC and DCC genes are present both in adenoma‐ and in carcinoma‐derived lines in this model, but the first evidence of an abnormality in the p53 gene was concomitant with the cells' ability to grow as a tumour in athymic nude mice. This genetic change coincided with the detection, by MRS, of UDP‐hexose (ribose moiety, 2D MRS cross peak between H2 at 4.38 ppm and HI at 5.99 ppm) and the appearance of an additional fucosyl resonance (cross peak between‐CH3 at 1.41 and H5 at 4.30 ppm) in the least tumori‐genic of the carcinoma cell lines. An increase in complexity of the fucosylation spectral pattern was observed with further cellular de‐differentiation and increased tumorigenicity. Collectively these data support the existence of an adenoma‐carcinoma sequence.
Selective interactions between mammary epithelial cells and fibroblasts in co‐culture
Authors: Adam Liana , Crepin Michel , Lelong Jean‐Claude , Spanakis Emmanuel , Israel Lucien 
Published: February 2007

AbstractParacrine interactions between breast‐cancer cells (MCF7) and stromal fibroblasts were studied in relation to the presence of steroid hormones, using co‐cultures in which the 2 populations were separated by a microporous membrane. Densities and DNA‐synthesis rates of the co‐existing populations were interrelated. Proliferation was, therefore, viewed as the cumulative result of several factors, some of which are non‐specific, e.g., are density‐dependent, and some are specifically related to the feeders' origin and/or to culture conditions. Specific effects were measured and evaluated by stepwise analysis of covariance. MCF7 stimulated proliferation of fibroblasts differentially. Malignant‐tumour fibroblasts were stimulated more than non‐pathological ones. The magnitude of these effects was dependent on the presence of steroids. A similar analytical method was used for evaluating differential stromal influences on 4 epithelial phenotypic characters commonly used as prognostic markers. The estrogen‐receptor, progesterone‐receptor, pS2 and cathepsine‐D phenotypes of MCF7, as well as their interrelations, were dependent on the origin of the fibroblasts, i.e., embryonic or adult, normal or tumoral.
Spatial distribution of mitosis, apoptosis and small blood vessels in malignant diffuse follicular‐center‐cell lymphomas: A nearest‐neighbor analysis
Authors: Kraft Rainer , Barbini Paolo , Leoncini Lorenzo , Del Vecchio Maria T. , Megha Tiziana , Minacci Chiara , Spina Donatella , Massai Maria R. , Tosi Piero , Laissue Jean A. , Cottier Hans 
Published: February 2007

AbstractTo better comprehend the relationships between cell birth and cell death in neoplastic disorders, the topography of these events needs to be considered. We applied a computerized nearest‐neighbor analysis to malignant, diffuse follicular‐center‐cell lymphomas in order to examine the spatial distribution of pyknotic (apoptotic) cells/bodies (A) and mitotic figures (M) in relation to capillaries (C) and venules (V). The results revealed a complex dispersion pattern, with significant aggregations of A and M, in addition to an even greater random distribution component. The greatest clustering displayed by A was around capillaries (A‐C, 42% reduction of object frequency between the first and second distance class), followed by A‐A (33%), A‐V (24%) and A‐M (12%). Additional values for mitotic figures were: M‐M (45%), M‐V (33%) and M‐C (22%). These findings may reflect the relative importance of inherent properties of the neoplastic and host factors, respectively, in the regulation of cell birth and cell death rates. © 1994 Wiley‐Liss, Inc.