bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of cutaneous melanoma associated with pigmentation characteristics and freckling: Systematic overview of 10 case‐control studies
Authors: Bliss Judith M. , Ford Deborah , Swerdlow Anthony J. , Armstrong Bruce K. , Cristofolini Mario , Elwood J. Mark , Green Adèle , Holly Elizabeth A. , Mack Thomas , Mackie Rona M. , ØSterlind Anne , Walter Stephen D. , Peto Julian , Easton Douglas F. 
Published: February 2007

AbstractUsing individual subject data from 10 case‐control studies, comprising over 3000 cases and almost 4000 controls, we have estimated the relative risk of melanoma associated with aspects of complexion, namely, hair, eye and skin colour and freckling in adulthood, and have examined the relationships between these factors and naevus count in terms of melanoma risk. Compared with individuals with black or dark brown hair, the relative risks for developing melanoma in those with light brown, blonde and red hair were 1.49 (95% Cl 1.31, 1.70), 1.84 (95% Cl 1.54, 2.21) and 2.38 (95% Cl 1.90, 2.97), respectively. Individuals with blue eyes had a risk 1.55 (95% Cl 1.35, 1.78) times that for those with brown eyes, or 1. 15 (95% Cl 0.94, 1.40) after adjusting for hair colour and freckling in adulthood. The relative risks associated with hair and eye colour were independent of those for naevus count and skin colour. Light skin colour and high freckle density were also highly significant risk factors, independent of each other and of naevus count and hair and eye colour. The risks associated with these factors, while individually modest, are largely independent, and thus pigmentation characteristics and freckling tendency should be useful in identifying high risk groups to be targeted for prevention. © 1995 Wiley‐Liss, Inc.
Detection and characterization of the prostate‐specific membrane antigen (PSMA) in tissue extracts and body fluids
Authors: Trover John K. , Beckett Mary Lou , Wright George L. 
Published: February 2007

AbstractThe prostate‐specific membrane antigen (PSMA) glycoprotein is recognized by the monoclonal antibody (MAb) 7EII ‐C5.3 as a predominant 100 kDa and minor 180 kDa component in LNCaP cell line extracts and its expression has been shown by immunohistochemistry to be highly restricted to prostate epithelium. The aim of the present study was to utilize Western blot analysis to determine if PSMA could be detected in human tissue extracts and body fluids and if so, which molecular forms were present. PSMA was detected as 120 and 200 kDa bands in normal, benign and malignant prostate tissues and seminal plasma. Further analysis demonstrated that the larger molecular form of PSMA may be a dimer of the lower m.w. species. The PSMA glycoprotein was not detected in the majority of non‐ prostate tissue extracts examined except for a low yet significant amount in normal salivary gland, brain and small intestine, suggesting that PSMA may not be as prostate‐specific as originally thought. Since the prostate‐specific antigen (PSA) has been shown to be maximally shed into the serum in high‐grade and metastatic prostate carcinomas, it was surprising that PSMA could not be detected in serum by Western blot analysis even in patients with actively progressive metastatic disease. Second generation antibodies generated against different epitopes may be required to determine if PSMA is shed into serum. Our results support the hypothesis that PSMA is a novel prostate biomarker. © 1995 Wiley‐Liss, Inc.
Reproductive and other factors and risk of epithelial ovarian cancer: An australian case‐control study
Authors: Purdie David , Green Adèle , Bain Christopher , Siskind Victor , Ward Bruce , Hacker Neville , Quinn Michael , Wright Gordon , Russell Peter , Susil Beatrice 
Published: February 2007

AbstractOf the few factors known to be associated with epithelial ovarian cancer, the most consistently observed relate to women's reproductive function, although even here uncertainties remain. We have undertaken a case‐control study involving personal interviews with over 1,600 women, the largest of its kind to date, to investigate further the associations between women's reproductive histories and other factors and the development of ovarian cancer. Cases were drawn from women diagnosed with epithelial ovarian cancer in 3 Australian states, Queensland, New South Wales and Victoria, between August 1990 and December 1993, and controls were drawn at random from the electoral roll, stratified by age and geographic region. Trained interviewers administered standard questionnaires to obtain detailed information about women's reproductive and contraceptive histories and other factors of interest, such as smoking and family history of ovarian or other cancer. Findings were based on data from 824 cases and 860 controls and confirmed the reduced risk of ovarian cancer associated with increasing parity and duration of use of the oral contraceptive pill (OCP), hysterectomy and tubal ligation. The strongest association of all was seen with use of the OCP for 10 years or more. An inverse association between ovarian cancer and age at first birth was observed, but this was not statistically significant. There were no associations between development of ovarian cancer and number of incomplete pregnancies, use of hormone replacement therapy or menstrual history. Among other factors considered, education after leaving school was negatively associated and high body mass index, family history of ovarian cancer, use of talc in the abdominal or perineal region and smoking were positively associated with occurrence of ovarian cancer. © 1995 Wiley‐Liss, Inc.
Expression of urokinase receptor in various stromal‐cell populations in human colon cancer: Immunoelectron microscopical analysis
Authors: Ohtani Haruo , Pyke Charles , Dan Ø Keld , Nagura Hiroshi 
Published: February 2007

AbstractThe host reaction is an important factor in the biological behavior of cancers. In human colon adenocarcinoma, stromal cells and some cancer cells express the urokinase receptor (uPAR), a molecule involved in the regulation of extracellular proteolysis. The present study reveals the identity of uPAR‐ expressing cell types and the subcellular localization of this molecule by immunoelectron microscopy in colon cancer. uPAR‐positive cells were most abundant at the invasive margin of colon cancer and were identified as macrophages, fibroblasts, neutrophilic and eosinophilic granulocytes, endothelial cells and cancer cells. Of these, the most numerous were macrophages with uPAR detected along the plasma membrane, in accordance with its function in plasminogen activation on the cell surface. Fibroblasts were labeled in the lumen of rough endoplas‐ mic reticulum, indicating its intracellular synthesis. Some granulocytes and endothelial cells expressed immunoreactivity along the plasma membranes. uPAR‐positive cancer cells were stained along the plasma membrane and in rough endoplasmic reticulum. These findings suggested that a variety of non‐malignant host cells play an important role in the plasmin‐mediated breakdown of the extracellular matrix at the invasive margin. © 1995 Wiley‐Liss, Inc.
in vivo effects of 4‐amidinoindan‐l‐one 2′‐amidinohydrazone (CGP 48664A) and α‐difluoromethylornithine (DFMO) on L1210 growth, cell‐cycle phase distribution and polyamine contents
Authors: Dorhout Bernard , Te Velde Roelf Jakob , Ferwerda Harri , Kingma Anneke W. , de Hoog Elly , Muskiet Frits A. J. 
Published: February 2007

AbstractWe studied the in vivo effects of 4‐amidinoindan‐l‐one 2′‐amidinohydrazone (CGP 48664A), α‐difluoromethylornithine (DFMO) and a combination of CGP 48664A‐DFMO on tumor growth, cell‐cycle phase distribution and polyamine contents. DBA‐2 mice were inoculated i.p. with 105 L1210 cells on day 0, treated i.p. on days 1–4 and killed on day 5. As compared to controls, CGP 48664A, DFMO and the CGP 48664A‐DFMO combination reduced L1210 cell numbers by 33, 43 and 85%, respectively. CGP 48664A did not affect cell‐cycle phase distribution. DFMO and the CGP 48664A‐DFMO combination caused a moderate and a heavy accumulation in G0/G1‐ and G2/M‐phases, respectively. Compared with controls, the CGP 48664A‐DFMO combination reduced putrescine, spermidine and total polyamines, but did not affect spermine. Compared with CGP 48664A, the CGP 48664A‐DFMO combination caused lower putrescine and total polyamines, higher spermine, but no change in spermidine. Compared with DFMO, the CGP 48664A‐DFMO combination caused higher putrescine and spermidine, lower spermine, but no change in total polyamine levels. We conclude that CGP 48664A potentiates the cystostatic effect of DFMO in vivo. The resulting growth inhibition is accompanied by an accumulation in G0/G1‐ and G2/M‐phases and a reduction of putrescine and spermidine. The data suggest that perturbed polyamine composition rather than reduced spermidine or total polyamine pool size causes a profound growth inhibition. © 1995 Wiley‐Liss, Inc.
Cyclophosphamide plus tumor necrosis factor‐α chemoimmunotherapy cured mice: Life‐long immunity and rejection of re‐implanted primary lymphoma
Authors: Ehrke M. Jane , Verstovšek Srdan , Krawczyk Christian M. , Ujházy Peter , Zaleskis Gintaras , Maccubbin Darbie L. , Mihich Enrico 
Published: February 2007

AbstractChanges in functionally and phenotypically definable spleno‐cyte subsets in aging mice which had been rendered tumor‐free in early life by immunochemotherapy (cyclophosphamide plus tumor necrosis factor‐α) were studied in the syngeneic EL4 lymphoma‐C57BL/6 murine model. Treatment‐induced long‐term survivors (LTS) surviving rechallenge are termed “immune‐LTS”. On day 120 (day 0, initial tumor inoculation), splenocytes from day 60 rechallenged immune‐LTS developed significantly greater specific anti‐EL4 cytolytic activity in an ex vitro assay than those from non‐rechallenged LTS. Splenocytes from combination‐treated groups developed significantly higher activity than those from cyclophosphamide‐induced immune‐LTS. The splenic effector precursor was a CD8+ T cell. The specific anti‐EL4 effector cell from the cyclophosphamide‐induced immune‐LTS was CD4− CD8+; however, approximately 50% of those from combination‐treated immune‐LTS appeared to be CD4+CD8+. On day 520 immune‐LTS were randomized into 2 groups. One group was re‐implanted with EL4 tumor; all mice survived. The other group was killed and, even though their splenocytes developed considerable anti‐EL4 activity, their allogeneic responsiveness was as reduced as that of age* matched controls. Phenotypic analysis, compared with splenocytes from young and age‐matched controls, revealed changes in the makeup of each T‐cell subset, except the CD4+CD8+, and all subsets, except the CD4− CD8−, had increases in CD44 positivity. On day 625, the age of these mice was equivalent to the median life‐span of C57BL/6 mice; nevertheless, their splenocytes developed high anti‐EL4 activity. Phenotypic analysis indicated that, compared to day 520, there was a major decrease in CD4− CD8+ splenocytes; we suggest that these cells had migrated to the site of tumor eradication.
EWS‐FLI‐1 and EWS‐ERG chimeric mRNAs in Ewing's sarcoma and primitive neuroectodermal tumor
Authors: Ida Kohmei , Kobayashi Shigetoshi , Taki Tomohiko , Hanada Ryoji , Bessho Fumio , Yamamori Shunji , Sugimoto Tohru , Ohki Misao , Hayashi Yasuhide 
Published: February 2007

AbstractThde t( 11;22)(q24;q 12) and t(21;22)(q22;q 12) are specific chromosomal translocations found in the Ewinhd family of tumors including ES, PNET and Askin tumors. In these translocations, the amino‐terminal portion of the EWS gene located in 22q 12 fuses to the carboxyl‐terminal portion of the FLI‐I gene located in 11 q24 or the ERG gene located in 21 q22, which belong to the ets oncogene super‐family of transcription activators. We investigated the chimeric mRNAs of 15 ESs (7 cell lines and 8 tumor samples) and 7 PNETs (3 cell lines and 4 tumor samples) using the RT‐PCR method and sequencing. We detected 2 types of EWS‐ERG chimeric mRNA in 2 ES cell lines and I PNET tumor sample in addition to 4 types of EWS‐FU‐1 chimeric mRNA in 11 ESs (4 cell lines and 7 tumor samples) and 4 PNETs (2 cell lines and 2 tumor samples). There seemed to be no association between the type of chimeric mRNA and clinical features such as sex, age, primary site and histopathology of the patients. All of the chimeric mRNAs are generated from in‐frame junctions and are thought to encode fusion proteins that may be the molecular mechanism involved in the Ewing family of tumors.
Specific targeting of a mutant, activated egf receptor found in glioblastoma using a monoclonal antibody
Authors: Hills David , Rowlinson‐Busza Gail , Gullick William J. 
Published: February 2007

AbstractA truncated epidermal growth factor receptor (EGFR) expressed from a rearranged and amplified EGFR gene is present at high frequency in gliomas. In this work we show that when this receptor is expressed in NIH3T3 fibroblasts it is partially activated and confers tumorigenicity to this cell line in vivo but no growth advantage in vitro anchorage‐independent growth assays. Because the mutation occurs in the extracellular domain of the receptor, it can be considered to represent a glioma‐specific tumour marker. Here we demonstrate that 2 monoclonal antibodies, DH 1.1 and DH8.3, raised to a synthetic peptide spanning the unique junctional sequence, can recognise the mutant receptor but not the normal receptor in both denatured and native states. Furthermore, radiolabelled antibody DH8.3 successfully targets tumours expressing this antigen in nude mice.
Prevention of prostate‐cancer metastasis in vivo by a novel synthetic inhibitor of urokinase‐type plasminogen activator (uPA)
Authors: Rabbani Shafaat , Harakidas Penelope , Davidson Donald J. , Henkin Jack , Mazar Andrew P. 
Published: February 2007

AbstractUrokinase‐type plasminogen activator (uPA) is a serine protease associated with tissue remodeling, cellular invasiveness, matrix degradation and tumor growth. Over‐expression of uPA by the rat prostate‐cancer cell line Dunning R3227, Mat LyLu, results in increased tumor metastasis to several non‐skeletal and skeletal sites. Histological examination of these skeletal lesions has shown them to be primarily osteoblastic. In the present study we examined the capacity of a selective inhibitor of uPA enzymatic activity, 4–iodo benzo[b]thiophene‐2–carbox‐amidine (B‐428), to prevent the development of tumor growth and invasiveness in a syngeneic model of rat prostate cancer using a Dunning R3227 cell line over‐expressing rat uPA. Male Copenhagen rats were inoculated s.c. with experimental cells into the right flank and continuously infused i.p. with either vehicle alone or uPA inhibitor for 2 to 3 weeks. Animals were killed at timed intervals and evaluated for the development of tumor growth and metastasis. Serum from these animals was collected to examine any signs of nephrotoxicity. Control animals receiving vehicle alone developed large tumors at the site of inoculation as well as macroscopic metastases in the lungs, kidney, spleen and lymph nodes. In contrast, experimental animals receiving uPA inhibitor showed a marked decrease in primary tumor volume and weight as well as in the development of tumor metastases. The occasional tumor metastases observed after infusion of B‐428 were significantly smaller than those observed in vehicle controls. These effects of B‐428 were found to be dose‐dependent without any adverse effects on the renal function of experimental animals. These studies demonstrate that uPA‐specific inhibitors can decrease primary tumor volume and invasiveness as well as metastasis in a model of prostate cancer where uPA has been implicated as a major pathogenetic factor. © 1995 Wiley‐Liss, Inc.
Allelic loss at 1p and 19q frequently occurs in association and may represent early oncogenic events in oligodendroglial tumors
Authors: Josefa Bello M. , Leone Paola E. , Vaquero Jesús , De Campos José M. , Elena Kusak M. , Sarasa José L. , Pestaña Angel , Rey Juan A. 
Published: February 2007

AbstractThe molecular mechanisms underlying the genesis and progression of oligodendroglial tumors are poorly understood, since only restricted information on loss of heterozygosity from isolated cases is available. The commonest alterations appear to involve deletion of 1p and 19q, while loss of heterozygosity for 9p, chromosome 10 or epidermal growth factor receptor gene amplification have been described in single tumors. We have applied restriction fragment length polymorphism analysis to 14 loci covering chromosome 1 and 7 loci on chromosome 19 in a series of 25 tumors with an oligodendroglial component to determine precisely the participation of these suppressor genes in the genesis of tumors. Twenty‐two and 19 of the 25 samples displayed LOH at 1p and 19q, respectively, and both anomalies were detected in association in 17 samples, including low‐ and high‐grade oligodendrogliomas as well as mixed oligo‐astrocytomas. Our findings suggest that inactivation of tumor suppressor genes located on 1p and 19q represent cooperative alterations occurring at early stages of oncogenic transformation of oligodendroglial neoplasms. © 1995 Wiley‐Liss, Inc.
E‐cadherin expression in bladder cancer using formalin‐fixed, paraffin‐embedded tissues: Correlation with histopathological grade, tumour stage and survival
Authors: Syrigos Konstantinos N. , Krausz Thomas , Waxman Jonathan , Pandha Hardev , Rowlinson‐Busza Gail , Verne Julia , Epenetos Agamemnon A. , Pignatelli Massimo 
Published: February 2007

AbstractTo determine the potential prognostic value of epithelial cadherin (E‐cadherin), a Ca2+‐dependent cell‐cell adhesion molecule, we have analysed its immunoreactivity and cellular localisation in 67 transitional cell carcinomas (TCC) using an avidin‐biotin immunoperoxidase technique on formalin‐fixed, paraffin‐embedded tissues. These results were correlated with histopathological grade, tumour stage, presence of metastases and survival. In addition, 10 cystitis and 11 normal bladder biopsies were evaluated as controls. E‐cadherin was expressed in a normal membranous pattern in all normal and 7 of 10 cystitis biopsies. Loss of normal surface E‐cadherin was expression was found in 3 of 15 superficial tumours and in 48 of 52 invasive cancers. Abnormal immunoreactivity was strictly related to tumour differentiation and stage. Fifteen of 20 well‐differentiated (grade 1) tumours showed preserved membranous E‐cadherin immunoreactivity, while 46 of 47 moderate and poorly differentiated tumours (grades II and III) demonstrated abnormal staining patterns. Loss of membranous E‐cadherin immuno‐reactivity was also associated with advanced tumour stage. There was a significantly higher 5‐year survival rate for patients with preserved membranous staining compared with patients with abnormal staining. © 1995 Wiley‐Liss, Inc.
In vitro differentiation of HT‐29 M6 mucus‐secreting colon cancer cells involves a trychostatin A and p27KIP1‐inducible transcriptional program of gene expression
Authors: Mayo Clara , Lloreta Josep , Real Francisco X. , Mayol Xavier 
Published: February 2007

AbstractTumor cell dedifferentiation—such as the loss of cell‐to‐cell adhesion in epithelial tumors—is associated with tumor progression. To better understand the mechanisms that maintain carcinoma cells in a differentiated state, we have dissected in vitro differentiation pathways in the mucus‐secretor HT‐29 M6 colon cancer cell line, which spontaneously differentiates in postconfluent cultures. By lowering the extracellular calcium concentration to levels that prevent intercellular adhesion and epithelial polarization, our results reveal that differentiation is calcium‐dependent and involves: (i) a process of cell cycle exit to G0 and (ii) the induction of a transcriptional program of differentiation gene expression (i.e., mucins MUC1 and MUC5AC, and the apical membrane peptidase DPPIV). In calcium‐deprived, non‐differentiated postconfluent cultures, differentiation gene promoters are repressed by a trichostatin A (TSA)‐sensitive mechanism, indicating that loss of gene expression by dedifferentiation is driven by histone deacetylases (HDAC). Since TSA treatment or extracellular calcium restoration allow gene promoter activation to similar levels, we suggest that induction of differentiation is one mechanism of HDAC inhibitor antitumor action. Moreover, transcriptional de‐repression can also be induced in non‐differentiating culture conditions by overexpressing the cyclin‐dependent kinase inhibitor p27KIP1, which is normally induced during spontaneous differentiation. Since p27KIP1 downregulation in colon cancer is associated with poor prognosis independently of tumor cell division rates, we propose that p27 KIP1 may prevent tumor progression by, at least in part, enhancing the expression of some differentiation genes. Therefore, the HT‐29 M6 model allows the identification of some basic mechanisms of cancer cell differentiation control, so far revealing HDAC and p27KIP1 as key regulatory factors of differentiation gene expression. J. Cell. Physiol. 212: 42–50, 2007. © 2007 Wiley‐Liss, Inc.
Transgenic mice expressing LHX3 transcription factor isoforms in the pituitary: Effects on the gonadotrope axis and sex‐specific reproductive disease
Authors: Savage Jesse J. , Mullen Rachel D. , Sloop Kyle W. , Colvin Stephanie C. , Camper Sally A. , Franklin Craig L. , Rhodes Simon J. 
Published: February 2007

AbstractThe LHX3 transcription factor plays critical roles in pituitary and nervous system development. Mutations in the human LHX3 gene cause severe hormone deficiency diseases. The gene produces two mRNAs which can be translated to three protein isoforms. The LHX3a protein contains a central region with LIM domains and a homeodomain, and a carboxyl terminus with the major transactivation domain. LHX3b is identical to LHX3a except that it has a different amino terminus. M2‐LHX3 lacks the amino terminus and LIM domains of LHX3a/b. In vitro experiments have demonstrated these three proteins have different biochemical and gene regulatory properties. Here, to investigate the effects of overexpression of LHX3 in vivo, the alpha glycoprotein subunit (αGSU) promoter was used to produce LHX3a, LHX3b, and M2‐LHX3 in the pituitary glands of transgenic mice. Alpha GSU‐beta galactosidase animals were generated as controls. Male αGSU‐LHX3a and αGSU‐LHX3b mice are infertile and die at a young age as a result of complications associated with obstructive uropathy including uremia. These animals have a reduced number of pituitary gonadotrope cells, low circulating gonadotropins, and possible sex hormone imbalance. Female αGSU‐LHX3a and αGSU‐LHX3b transgenic mice are viable but have reduced fertility. By contrast, αGSU‐M2‐LHX3 mice and control mice expressing beta galactosidase are reproductively unaffected. These overexpression studies provide insights into the properties of LHX3 during pituitary development and highlight the importance of this factor in reproductive physiology. J. Cell. Physiol. 212: 105–117, 2007. © 2007 Wiley‐Liss, Inc.