bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the level of mRNA expression of the membrane regulators of complement, CD59, CD55 and CD46, in breast cancer
Authors: Rushmere Neil K. , Knowlden Janice M. , Gee Julia M.W. , Harper Maureen E. , Robertson John F. , Morgan B. Paul , Nicholson Robert I. 
Published: January 2004

AbstractWe have examined the relative mRNA expression of the complement (C) regulatory proteins CD59, CD55 and CD46 in RNA isolated from 50 primary breast cancer specimens using a semiquantitative RT‐PCR approach. Having normalized the mRNA expression levels of the C regulators relative to actin, we subsequently correlated their expression with estrogen receptor (ER) and various clinical, pathologic and biochemical features of the disease. CD59 and CD46 were detected in all clinical biopsies, while CD55 mRNA was detected in the majority of samples. The comparative levels of expression between the 3 regulators analyzed, using Spearman rank correlation test, revealed a significant association (p = 0.01; r = 0.36) between CD46 and CD59. CD46 exhibited the most striking pattern of association, with increased levels of expression being associated with ER‐positive samples and lower levels of expression associated with a loss of differentiation and epidermal growth factor receptor positivity. Application of Spearman rank correlation test revealed CD46 expression was significantly associated with expression of ER at the level of protein (p = 0.031; r = 0.31) and mRNA (p < 0.001; r = 0.52). CD46 expression also correlated with insulin‐like growth factor receptor‐positive samples using Spearman rank correlation test (p = 0.016; r = 0.34), but negatively associated with tumor samples either exhibiting histologic grade 3 when compared to grades 1 or 2 or displaying elevated levels of inflammatory cell infiltrate. Immunohistochemical analysis of a limited series (n = 8) of paraffin‐embedded breast cancers indicated that the level of CD46 protein expression directly associates with that of the mRNA and, where prominent, is localized in the tumor epithelial cell population, including at the plasma membrane. These data provide new information on expression of these important regulators in breast cancer and suggest that CD46 should be evaluated as a novel prognostic indicator. © 2003 Wiley‐Liss, Inc.
Expression of sperm protein 17 (Sp17) in ovarian cancer
Authors: Straughn J. Michael , Shaw Denise R. , Guerrero Antonio , Bhoola Snehal M. , Racelis Alicia , Wang Zhiqing , Chiriva‐Internati Maurizio , Grizzle William E. , Alvarez Ronald D. , Lim Seah H. , Strong Theresa V. 
Published: January 2004

AbstractSperm protein 17 (Sp17) is an antigenic protein highly expressed in spermatozoa. Sp17 expression was demonstrated recently in multiple myeloma, suggesting that it may be a novel cancer‐testis antigen. Expression of Sp17 mRNA and protein was examined in human ovarian tumors. Sp17 mRNA was evaluated by reverse transcription‐polymerase chain reaction (RT‐PCR) and Northern blot analysis of RNA derived from epithelial ovarian tumors and normal tissues. RT‐PCR analysis detected Sp17 transcripts in 15 of 18 (83%) primary ovarian tumors. The transcript was not detected in RNA derived from normal uterus or cervix, whereas weak expression was noted in some normal ovarian tissue samples. Northern blot analysis showed no detectable Sp17 mRNA expression in normal tissues, including normal ovary, but showed Sp17 expression in 17 of 25 ovarian tumors (68%). To evaluate protein expression, mouse monoclonal antibodies were produced against recombinant Sp17 protein and used in Western blot and immunohistochemical analyses of normal reproductive tissue and primary ovarian tumor samples. Sp17 protein was detected by Western blot analysis in normal spermatozoa and in 8 of 19 ovarian tumor samples. Immunohistochemical studies showed Sp17 expression in spermatozoa, ciliated cells of the female reproductive tract, and most ovarian tumors evaluated. Tumors showed a predominately nuclear localization of Sp17 expression, with some cytoplasmic staining. These results demonstrate that Sp17, a protein with restricted expression in somatic tissues, is expressed in ovarian tumors. Because Sp17 is immunogenic, it may represent a novel target for immunotherapeutic interventions for ovarian cancer patients. © 2003 Wiley‐Liss, Inc.
Screen‐detected prostate cancer and the insulin‐like growth factor axis: Results of a population‐based case‐control study
Authors: Oliver Steven E. , Gunnell David , Donovan Jenny , Peters Tim J. , Persad Raj , Gillatt David , Pearce Anya , Neal David E. , Hamdy Freddie C. , Holly Jeff 
Published: January 2004

AbstractHigher circulating levels of IGF‐I have been associated with increased risk of prostate and some other cancers. Most research on prostate cancer has been based on men with symptoms or identified following treatment of benign disease. However, increasing numbers of cancer cases are now detected in asymptomatic men following prostate‐specific antigen (PSA) tests. We therefore used a population‐based case‐finding exercise using the PSA test to examine whether associations between the IGF axis and cancer risk were apparent in this population. A matched case‐control study was conducted among 7,383 men (50–70 years) receiving a PSA test as part of a case‐finding exercise. Assays of IGF‐I, IGF‐II, IGFBP‐2 and IGFBP‐3 were performed on cases and 2 controls matched on age, recruitment center and calendar time. Analyses were based on 176 cases and 324 matched controls. The risk of prostate cancer increased across quartiles of IGF‐I (highest vs. lowest quartile, OR = 2.34; 95% CI = 1.26–4.34; ptrend = 0.02) and IGF‐II (OR = 1.78; 95% CI = 0.94–3.15; ptrend = 0.09). Controlling for smoking history and IGFBP‐3 strengthened associations with cancer for both IGF‐I (OR = 3.00; 95% CI = 1.50–6.01; ptrend 0.005) and IGF‐II (OR = 2.02; 95% CI = 1.07–3.84; ptrend = 0.04) Associations between the IGFs and cancer risk were stronger for advanced cases. Our findings suggest that both IGF‐I and IGF‐II are associated with an increased risk of screen‐detected prostate cancer. © 2003 Wiley‐Liss, Inc.
HLA‐B35‐restricted immune responses against survivin in cancer patients
Authors: Reker Sine , Becker Jürgen C. , Svane Inge Marie , Ralfkiaer Elisabeth , Straten Per thor , Andersen Mads Hald 
Published: January 2004

AbstractTwo HLA‐A2 restricted epitopes have recently been identified from the broadly expressed tumor antigen survivin, and several vaccination trials in cancer patients based on these survivin‐derived peptides have been initiated. Consequently, there is a crucial need for the identification of survivin epitopes restricted to other HLA‐molecules in order to extend the proportion of patients that can enter these ongoing clinical trials. In the present study, we characterized 2 survivin‐derived epitopes, which are restricted to HLA‐B35. Specific T‐cell reactivity against these survivin‐derived epitopes was found in the peripheral blood from patients with different B‐cell malignancies and melanoma. Substitution of the C‐terminal anchor residue of the survivin‐derived peptides improved the recognition by tumor‐infiltrating lymphocytes from melanoma patients. Furthermore, we demonstrated spontaneous cytotoxic T‐cell responses to survivin in a primary melanoma lesion. The characterization of these epitopes allows more patients can be included in the ongoing peptide‐based survivin vaccination trials against cancer. © 2003 Wiley‐Liss, Inc.
Soft‐tissue sarcoma and dioxin: A case‐control study
Authors: Tuomisto Jouni T. , Pekkanen Juha , Kiviranta Hannu , Tukiainen Erkki , Vartiainen Terttu , Tuomisto Jouko 
Published: January 2004

AbstractSoft‐tissue sarcoma has been proposed to be a candidate for a dioxin‐induced cancer. However, previous epidemiologic studies have suffered from poor exposure data and mixed exposures. We studied the association between sarcoma risk and individually estimated dioxin exposure in a general population exposed to relatively low levels of dioxin via food. A multicenter prospective case‐control study was conducted in 4 university hospitals and 12 other hospitals in southern Finland. Participants included 110 patients with soft‐tissue sarcoma (cases) and 227 area‐ and age‐matched controls. Controls were patients operated for appendicitis. Individual dioxin concentrations were analyzed from subcutaneous fat samples by gas chromatography‐mass spectrometry. The average (range) dioxin concentration was 33.4 (4.4–145.5) ng/kg (toxic equivalencies in fat according to WHO). No increased risk associated with increased dioxin concentration was observed. In contrast, the highest risk of sarcoma was found at low levels of dioxin. Odds ratios for different quintiles as compared with the lowest quintile of dioxins (median, 11.5 ng/kg) varied from 0.43 (95% CI = 0.18–1.05) to 0.65 (95% CI = 0.22–1.95). The result was little affected by studied confounders and the findings were similar for different sarcoma subtypes, age groups and study areas. The results imply that dioxin does not increase the risk of soft‐tissue sarcoma at the present population levels. © 2003 Wiley‐Liss, Inc.
Fine mapping of chromosome 22q tumor suppressor gene candidate regions in astrocytoma
Authors: Hartmann Christian , Nümann Astrid , Mueller Wolf , Holtkamp Nikola , Simon Matthias , von Deimling Andreas 
Published: January 2004

AbstractAstrocytomas and glioblastomas are the most frequent primary brain tumors in adults. Mutations and altered expression of multiple genes have been found to contribute to the genesis of these tumors. However, many factors in the genesis of astrocytic gliomas are not resolved yet. The frequent losses on several chromosomes indicate the role of still unidentified tumor suppressor genes. Loss of heterozygosity (LOH) on 22q has been described in up to 30% of astrocytic tumors and may be associated with progression to anaplasia. In a first step, information from the nearly finished physical sequence of chromosome 22 were used to map LOH data from 22q deletion studies on different tumor entities to identify potential tumor suppressor gene candidate regions. Next, a series of 153 astrocytic gliomas was examined with 11 polymorphic markers spanning these regions. Forty‐nine (32%) astrocytic gliomas exhibited LOH on 22q, 17 (35%) of which lost heterozygosity for all markers and 32 (65%) of which carried interstitial or partial deletions. Two regions were identified on the physical DNA sequence. The centromeric region spans 3 Mb and the telomeric region 2.7 Mb. The reduced size of these regions now allows direct analysis of all genes included. We already performed mutation analysis on 4 candidate genes from these regions (MYO18B, DJ1042K10.2, MKL1 and EP300), but did not find any mutations in astrocytic tumors. © 2003 Wiley‐Liss, Inc.
Nadir prostate‐specific antigen best predicts the progression to androgen‐independent prostate cancer
Authors: Morote Juan , Trilla Enrique , Esquena Salvador , Abascal José María , Reventos Jaume 
Published: January 2004

AbstractThe objective of our study was to analyze the value of prostate‐specific antigen (PSA) levels before and after androgen suppression to predict the time to androgen‐independent progression (AIP) in patients with advanced and metastatic prostate cancer. A series of 283 prostate cancer patients under androgen suppression as a single treatment was studied. The disease was locally advanced in 98 patients and metastatic in the remainder 185. AIP was defined after 2 consecutive increases of serum PSA after the nadir value. The mean follow‐up before AIP was 29.2 months (3–198). AIP was detected in 205 patients (72.4%). In 152 patients (74.1%), the event was detected within 24 months, while in 53 patients (25.9%), it was observed beyond 24 months. The multivariate analysis showed that the nadir PSA and the time to reach the nadir PSA were the most significant predictors of the time to AIP. The odds ratio of having a biochemical response greater than 24 months was 20 times higher in patients that achieved an undetectable PSA level of 0.2 ng/mL or less. Moreover in those patients whose nadir PSA reached beyond 12 months after androgen suppression the odds ratio was 18 times higher. These results show that the ability to achieve an undetectable nadir PSA and the time to reach it are the most significant predictors of the time to AIP in patients with locally advanced and metastatic prostate cancer under androgen suppression as a single therapy. © 2003 Wiley‐Liss, Inc.
Enhanced radiosensitization and chemosensitization in NF‐κB‐suppressed human oral cancer cells via the inhibition of γ‐irradiation‐ and 5‐FU‐induced production of IL‐6 and IL‐8
Authors: Tamatani Tetsuya , Azuma Masayuki , Ashida Yuki , Motegi Katsumi , Takashima Rina , Harada Koji , Kawaguchi Shin‐ichi , Sato Mitsunobu 
Published: January 2004

AbstractWe examined the mechanisms underlying the enhancement of radiosensitivity and chemosensitivity to γ‐irradiation (IR) and 5‐Fluorouracil (5‐FU) in human oral carcinoma cells (B88) in which NF‐κB activity was constitutively suppressed. Three super‐repressor form of IκBα cDNA‐transfected cell (B88mI) clones and 1 empty vector‐transfected cell clone (B88neo) have been established. We found that the tumor‐forming ability in nude mice of B88mI clones was significantly lower than that of B88 or B88neo. This suppressed ability in tumorigenicity was attributed to the down‐regulation of the expression of interleukin (IL)‐1α, IL‐6, IL‐8, vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)‐9 in B88mI cell clones as compared to that in B88 or B88neo. IR and 5‐FU induced a much greater degree of apoptosis, as evidenced by flow cytometry analysis and annexin V staining, in B88mI cell clones than in B88 or B88neo. When tumor‐bearing nude mice were treated with IR or 5‐FU, the suppression of tumor growth was significantly augmented in B88mI cell clones as compared to that in B88 or B88neo. ELISA analysis indicated that although a remarkable increase in production of IL‐6 and IL‐8 was observed in B88 and B88neo after in vitro exposure to IR or treatment with 5‐FU, radiotherapy and chemotherapy‐induced production of these cytokines was significantly suppressed in B88mI cell clones. These findings suggest that production of angiogenic factors and growth factors in response to radiotherapy and chemotherapy is a principal mechanism of inducible radioresistance and chemoresistance in human oral cancers, and establish the inhibition of NF‐κB as a rational approach to improve conventional radiotherapy and chemotherapy outcomes. © 2003 Wiley‐Liss, Inc.
Heterozygote deficiency in thymidylate synthase enhancer region polymorphism genotype distribution in Hungarian colorectal cancer patients
Authors: Adleff Vilmos , Hitre Erika , Köves István , Orosz Zsolt , Hajnal Anna , Kralovánszky Judit 
Published: January 2004

AbstractThymidylate synthase (TS) gene polymorphisms are important as prognostic factors in cancer chemotherapy, but recent results describe that the TS enhancer region (TSER) polymorphic genotypes may also modulate risk for malignancies. Two functionally important and ethnically diverse polymorphisms are present on the TS transcript, TSER, a repeat polymorphism (2 or 3 repeats; 2R, 3R) affecting TS expression, and a 6 bp ins/del polymorphism on the 3′ UTR (position TS1494, del6 or ins6), which may influence mRNA stability. Hungarian population has one of the highest colorectal cancer (CRC) mortality rates in Europe, and several elevated dietary risk factors affect a large part of the population. In our study (99 primary CRC cases), population analysis of the patient group genotype frequencies revealed a departure from the Hardy‐Weinberg equilibrium and significant heterozygote deficiency (p < 0.05) at the TSER locus. Despite the strong linkage between the 2 polymorphic loci, case TS1494del genotype frequencies were normally distributed, as well as the genotype frequencies of the healthy control population (n = 102), at both loci. Case‐control comparison demonstrated a lower relative risk of TSER heterozygotes (OR = 0.47; CI = 0.27–0.83; p = 0.008) and a possible higher prevalence of the 3R3R&ins6/del6 in the CRC group. The observation that heterozygotes are those less susceptible for CRC in the Hungarian population may support the possibility of 2 different pathways in which TS may play a role in colorectal carcinogenesis, probably nutrient (or folate)‐dependently. The lack of similar genotype effect seen with TS1494del polymorphism and the increased presence of one genotype combination (3R3R&ins6/del6) in the patient group suggest a possible TS haplotype effect influencing CRC risk. © 2003 Wiley‐Liss, Inc.
Guanine nucleotide depletion triggers cell cycle arrest and apoptosis in human neuroblastoma cell lines
Authors: Messina Elisa , Gazzaniga Paola , Micheli Vanna , Guaglianone Maria Rosaria , Barbato Silvia , Morrone Stefania , Frati Luigi , Aglianò Anna Maria , Giacomello Alessandro 
Published: January 2004

AbstractMycophenolic acid (MPA) specifically inhibits inosine‐5′‐monophosphate dehydrogenase, the first committed step toward GMP biosynthesis. In its morpholinoethyl ester pro‐drug form it is one of the most promising immunosuppressive drugs recently developed. The aim of the present study was to investigate the in vitro effects of MPA, at concentrations readily attainable during immunosuppressive therapy, on 3 human neuroblastoma cell lines (LAN5, SHEP and IMR32). Mycophenolic acid (0.1–10 μM) caused a decrease of intracellular levels of guanine nucleotides, a G1 arrest and a time‐ and dose‐dependent death by apoptosis. These effects, associated with an up‐regulation of p53, p21 and bax, a shuttling of p53 protein into the nucleus and a down‐regulation of bcl‐2, survivin and p27 protein, were reversed by the simultaneous addition of guanine or guanosine and were more evident using nondialysed serum containing hypoxanthine. These results suggest that in neuroblastoma cell lines clinically attainable concentrations of mycophenolic acid deplete guanine nucleotide pools triggering G1 arrest and apoptosis through p53‐mediated pathways, indicating a potential role of its morpholinoethyl ester pro‐drug in the management of patients with neuroectodermal tumors. © 2003 Wiley‐Liss, Inc.
Human papillomavirus (HPV) type 16‐specific CD8+ T cell responses in women with high grade vulvar intraepithelial neoplasia
Authors: Todd Richard W. , Roberts Sally , Mann Christopher H. , Luesley David M. , Gallimore Phillip H. , Steele Jane C. 
Published: January 2004

AbstractHuman papillomavirus (HPV)‐associated vulvar intraepithelial neoplasia (VIN) has serious sequelae for the sufferer. Current treatments are associated with poor response and high relapse rates. The development of HPV‐specific T cell immunotherapies offers a new approach to treatment. This will require a detailed understanding of the spectrum of T cell responses induced by HPV antigens, and how effectively viral antigens can be accessed by the immune system. We have investigated the frequency and spectrum of HPV16‐specific CD8+ T cell responses to three HPV16 antigens in 9 women with high grade VIN (VIN3). CD4‐depleted populations of responder cells were screened against overlapping 30–35mer peptides covering the sequences of HPV16 E6, E7 and E4 using ELISPOT assays of IFN‐γ release. We demonstrated CD8+ T cell reactivity to one or more of the proteins in 6 of 9 patient samples. All 6 of these responders recognised peptides covering the E7 protein, 3 of 9 women responded to E6 peptides, but no reactivity was seen to E4. Our results suggest that HPV16‐specific cytotoxic T cells (CTLs) are relatively common in women with persistent VIN3. The HPV‐specific CTL response, however, seems to be ineffective. There is some evidence that there are problems associated with the processing and presentation of HPV antigens by the infected vulvar epithelium. It will be crucial to address this in the design of any T cell based therapy for HPV‐associated VIN and vulval cancer. © 2003 Wiley‐Liss, Inc.
Significance of COX‐2 expression in human renal cell carcinoma cell lines
Authors: Chen Qinzhong , Shinohara Nobuo , Abe Takashige , Watanabe Takafumi , Nonomura Katsuya , Koyanagi Tomohiko 
Published: January 2004

AbstractAccumulating evidences indicate that cyclooxygenase (COX)‐2 plays an important role in tumorigenesis in many human cancers. Yet the relationship between COX‐2 and human renal cell carcinoma (RCC) remains unclear. The aim of our study was to evaluate COX‐2 expression in human RCC cell lines and its role in tumorigenesis of human RCC. Among the human RCC cell lines (SMKT‐R4, OS‐RC‐2, ACHN) and normal renal cell line RPTEC, COX‐2 overexpression was found in OS‐RC‐2 cells both at mRNA and protein levels. COX‐2 sense‐ and antisense‐orientated vectors were constructed and transferred into RCC cells. Significant suppression of cellular proliferation was demonstrated in OS‐RC‐2 antisense transfectants, whereas promotion was found in SMKT‐R4 sense transfectants by colony‐forming assay despite the observation that COX‐2 specific inhibitor NS398 exhibited similar IC50 among RCC cell lines by MTT assay. In comparison with parent cells and sense transfectants, significant suppression of COX‐2 expression and PGE2 production and increase in butyrate‐induced apoptosis were observed in OS‐RC‐2 antisense transfectants by Western blot, ELISA assay and FACS analysis, respectively. Furthermore, tumor growth and angiogenesis of OS‐RC‐2 antisense transfectants in nude mice was significantly suppressed and the survival time of these mice was significantly prolonged. Our study demonstrates that COX‐2 is overexpressed in OS‐RC‐2 RCC cell line and plays an important role in tumorigenesis of the cells in vivo, which implies that COX‐2 may be a therapeutic target for COX‐2‐expressing RCC, and that suppression of COX‐2 expression by antisense‐based strategy may have potential utility in treatment of COX‐2‐expressing RCC. © 2003 Wiley‐Liss, Inc.
Differential gene‐expression profiling in the leukemia cell lines derived from indolent and aggressive phases of CD56+ T‐cell large granular lymphocyte leukemia
Authors: Daibata Masanori , Matsuo Yoshinobu , Machida Hisanori , Taguchi Takahiro , Ohtsuki Yuji , Taguchi Hirokuni 
Published: January 2004

AbstractAs a rule, T cell large granular lymphocyte (T‐LGL) leukemia runs a chronic clinical course without need for therapy. Some cases, however, progress to an aggressive disease after the indolent clinical stage. The transformation mechanism into a high‐grade malignancy has not been well studied. We have established 2 leukemia cell lines, MOTN‐1 and PLT‐2, derived from the same clone of CD56+ T‐LGL leukemia in chronic and aggressive phases, respectively. The paired availability of such cell lines is valuable in biologic and genetic investigation of T‐LGL leukemia. We used a microarray containing 406 cDNAs to elucidate alterations of gene expression between the 2 cell lines. We found a number of genes that were differentially expressed: 13 genes with increased expression and 3 genes with reduced expression in PLT‐2 cells as compared to MOTN‐1 cells. Increased expression of the dek, rac, Op18, CD6, CD58, CD106, Id2, ATF4, IRF5, ELL2 and D6 genes, and reduced expression of the GzmA and GzmK genes were confirmed by real‐time quantitative reverse transcription‐PCR, whose results paralleled the microarray data. These upregulated genes encode oncoproteins, cell surface antigens including molecules related to T cell proliferation, transcription factors, and a chemokine receptor. The two downregulated genes encode granzymes that play an important role for induction of cell death. These findings suggest that there is differential gene expression in different clinical phases of T‐LGL leukemia and these differentially expressed genes would be potential targets for further studies to identify the genes involved in the transformation process of T‐LGL leukemia. © 2003 Wiley‐Liss, Inc.