bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of frizzled‐related protein and Wnt‐signalling molecules in invasive human breast tumours
Authors: Wong Sze Chuen Cesar , Lo Siu Fong Elena , Lee King Chung , Yam Judy W. P. , Chan John K. C. , Wendy Hsiao W. L. 
Published: October 2002

AbstractFrizzled‐related protein (Frp) is a new family of secreted proteins that contain a region homologous to the extracellular cysteine‐rich domain (CRD) of the frizzled family proteins. The role of Frp protein is far from clear. To explore the role of Frp and its relationship to the Wnt‐signalling pathway in breast cancer, in situ hybridization and immunohistochemical analyses of Frp, Wnt‐1, APC, β‐catenin, and its target genes c‐myc and cyclin D1 were conducted in 70 specimens of invasive ductal carcinomas of the human breast. Frp mRNA was down‐regulated in 62 and elevated in eight tumour specimens, compared with adjacent normal tissues. In the course of tumour progression, however, Frp mRNA steadily increased in both tumour and the adjacent tissues. Interestingly, the number of cases with axillary lymph node metastasis was significantly lower in the group with elevated Frp than in the group with decreased Frp, suggesting that Frp may contribute as a prognostic factor in invasive breast cancer. Wnt‐1, a gene implicated in human breast cancer, was markedly elevated in grade 1 tumours, but declined as tumour grade declined. The level of Wnt‐1 was linearly correlated with its downstream target β‐catenin (p<0.05), but was inversely correlated with Frp (p<0.05), suggesting a possible negative regulatory role of Frp with regard to Wnt‐1. APC was inversely correlated with β‐catenin (p<0.05). β‐catenin, a key transcriptional activator responsible for the activation of both c‐myc and cyclin D1 in colorectal tumours, was detected at high levels in the plasma membranes of cells in normal tissue. In tumour masses, however, β‐catenin lost its tight association with the membrane and diffused into the cytoplasm. Surprisingly, it clearly did not penetrate the nuclei, despite the fact that both c‐myc and cyclin D1 were markedly elevated in all tumour tissues. As revealed in this study, Wnt‐1/β‐catenin plays very different roles in the oncogenesis of breast and colon cancers. This first systemic analysis of the Frp and the Wnt‐signalling pathway in human breast cancer provides a springboard for further work on the role of Frp in the development of breast cancer. Copyright © 2001 John Wiley & Sons, Ltd.
APC mutations in synovial sarcoma
Authors: Saito Tsuyoshi , Oda Yoshinao , Sakamoto Akio , Kawaguchi Ken‐ichi , Tanaka Kazuhiro , Matsuda Shuichi , Tamiya Sadafumi , Iwamoto Yukihide , Tsuneyoshi Masazumi 
Published: October 2002

AbstractIt has previously been demonstrated that accumulated β‐catenin serves as an oncoprotein in synovial sarcoma and results in a poor overall survival rate, but the frequency of β‐catenin mutation was quite low (8.2%). The present study, using essentially the same study group of cases, screened for genetic alterations in the mutation cluster region (MCR) of the APC gene in 49 cases of synovial sarcoma. SSCP analysis followed by DNA direct sequencing revealed five missense APC mutations in four cases of synovial sarcoma (8.2%). The mutational sites comprised one case each at codons 1299 (GCT to ACT, Ala to Thr), 1412 (GGA to AGA, Gly to Arg), and 1414 (GTA to ATA, Val to Ile), in addition to one case with double point mutations at codon 1398 (AGT to AAT, Ser to Asn) and at codon 1413 (ATG to ATA, Met to Ile), together with β‐catenin mutation at codon 32 (GAC to TAC, Asp to Tyr). All four cases with APC mutations were histologically of the monophasic fibrous type and showed β‐catenin accumulation. All three cases with APC mutations available for follow‐up data were long survivors. This study provides the first evidence that APC mutations also occur in the field of sarcoma, especially in synovial sarcoma. Copyright © 2002 John Wiley & Sons, Ltd.
Correlation between localization, age, and chromosomal imbalances in ependymal tumours as detected by CGH
Authors: Jeuken Judith W. M. , Sprenger Sandra H. E. , Gilhuis Job , Teepen Hans L. J. M. , Grotenhuis Andre J. , Wesseling Pieter 
Published: October 2002

AbstractEpendymal tumours (ETs) are gliomas that arise from the ependymal lining of the cerebral ventricles and from the remnants of the central canal of the spinal cord. Both clinical and genetic studies suggest that distinct genetic subtypes of ETs exist, the subtypes being correlated with patient age and/or tumour site. In the present study, the tumour genome of 20 ETs (15 adult and five paediatric cases) was screened for chromosomal imbalances by comparative genomic hybridization (CGH). The most frequently detected imbalances were −22q (75%), −10q (65%), −21 (50%), −16p (50%), −1p (45%), +4q (45%), −10p (45%), −2q (40%), −6 (40%), −19 (40%), −2p (35%), −3p (35%), and −16q (35%). Comparison of the chromosomal imbalances detected in ETs with those previously reported in oligodendroglial and astrocytic tumours revealed that in this respect ETs show similarities to these other gliomas. By combining these results with those of a recent study of Zheng et al. and Hirose et al., it was found that although ETs from different sites and from adult and paediatric patients show overlap at the CGH level, some chromosomal imbalances occur predominantly in a certain category. In adult patients, spinal ETs relatively often showed +2, +7, +12, and −14q; infratentorial ETs −22; and supratentorial ETs −9. In addition, in posterior fossa ETs, −6 and +9 were much more frequent in adults than in children. It is concluded that the genetic background of ETs is complex and partly determined by tumour site, histopathological subtype, and age of the patient. Copyright © 2002 John Wiley & Sons, Ltd.
Transient P‐cadherin expression in radiation proctitis; a model of mucosal injury and repair
Authors: Hardy Robert G. , Brown Rachel M. , Miller Sarah J. , Tselepis Chris , Morton Dion G. , Jankowski Janusz A. Z. , Scott A. Sanders D. 
Published: October 2002

AbstractMorphology at both cellular and glandular levels in the colon is dependent to an extent on cell–cell adhesion mediated by cadherin–catenin complexes. Alterations in the expression of E‐cadherin, the cadherin normally present in colon, have been shown to be implicated in tissue remodelling within the gastrointestinal tract. Furthermore, it has previously been shown that P‐cadherin, normally present only in stratified epithelia and placenta, is expressed in colitis and during neoplastic change in the colon. The morphological features of mucosal injury induced by pre‐operative radiotherapy in the non‐neoplastic rectal mucosa were studied in patients with rectal adenocarcinoma. Three characteristic phases of radiation proctitis were defined on histological grounds (acute injury, and early and late regenerative phases) essentially correlating with the time interval between radiotherapy and surgery; such features were mirrored by alterations in cadherin–catenin expression and localization in rectal crypts. On immunohistochemistry and western blotting, P‐cadherin was highly expressed in the acute injury and early regenerative phases, with a decreased level of expression during late regeneration. E‐cadherin and associated catenins were translocated from membrane to cytoplasm in degenerating crypts, with return of normal membranous expression in regenerating crypts. In conclusion, radiation‐induced proctitis represents an in vivo model of mucosal injury and regeneration and provides a valid model in which to study events during epithelial injury and repair. Altered cadherin expression, in particular transient aberrant P‐cadherin expression, is intimately associated with these processes. Copyright © 2002 John Wiley & Sons, Ltd.
Expression of CXC chemokine IP‐10 in testicular germ cell tumours
Authors: Schweyer S. , Soruri A. , Baumhoer D. , Peters J. , Cattaruzza M. , Radzun H. J. , Fayyazi A. 
Published: October 2002

AbstractTumour‐infiltrating T lymphocytes (TILs) possess discrepant properties ranging from anti‐ to pro‐tumour activities. Understanding precisely which mechanisms navigating T lymphocytes into the tumour site will help to further the anti‐tumour or to disrupt the pro‐tumour activities of TILs. The present study asked what enables TILs to migrate into testicular germ cell tumours (TGCTs). TILs were characterized and the expression of a large panel of T‐lymphocyte‐attracting chemokines was investigated in 21 TGCT cases. Flow cytometry revealed that ≈80% of TGCT‐infiltrating T lymphocytes express CXCR3, a receptor for the chemokine interferon‐inducible protein‐10 (IP‐10). RT‐PCR and immunohistochemistry indicated that IP‐10 was the only chemokine investigated which was constantly expressed in TGCT. As IP‐10 was found to be expressed by endothelial cells of TGCT‐associated blood vessels, the question arose whether the IP‐10‐regulating cytokine interferon‐γ (IFNγ) is produced by tumour cells and if so, whether tumour‐derived IFNγ can induce IP‐10 in endothelial cells. Applying in situ hybridization, IFNγ transcripts were found in neoplastic germ cells. Analyses of two TGCT cell lines indicated that the tumour cells not only express IFNγ mRNA, but also produce and secrete IFNγ protein; tumour‐derived IFNγ provokes IP‐10 expression and secretion by endothelial cells in vitro, as assessed by PCR and ELISA. Together, the data suggest that neoplastic germ cells secret IFNγ and thereby stimulate tumour‐associated endothelial cells to express IP‐10, which contributes to the recruitment of CXCR3+ T lymphocytes to the site of TGCTs. Copyright © 2002 John Wiley & Sons, Ltd.
Radiotherapy and rectal cancer
Authors: Scott N. 
Published: October 2002

AbstractPre‐operative radiotherapy is being used to reduce local recurrence and improve survival following surgery for rectal cancer. A report by Nagtegaal et al. analyses the histopathological effects in a large, randomized study employing short course radiotherapy. In future, changes in some of these tumour parameters will have to be considered when auditing rectal cancer resections and identifying prognostic factors. Copyright © 2002 John Wiley & Sons, Ltd.
Loss of heterozygosity in the clonal evolution of flat colorectal neoplasms
Authors: Fujii Hiroaki , Ajioka Yoichi , Kazami Shinsuke , Takagaki Tetsuya , Gong Zhu Xue , Hirose Sachiko , Watanabe Hidenobu , Shirai Toshikazu 
Published: October 2002

AbstractIn contrast to invasive colorectal carcinomas that develop in typical exophytic adenoma–carcinoma sequences, some invasive cancers may evolve from flat mucosal dysplastic lesions. Despite their relatively small size, these flat colorectal lesions are often associated with high‐grade dysplasia and may show an aggressive clinical course. To delineate the genetic pathways in the clonal evolution of these tumors, multiple foci were microdissected from 13 cases and the allelic deletions of 15 chromosomal arms were analysed. Loss of heterozygosity (LOH) was detected most frequently on 17p (77%), followed by 18q (69%), and 5q (54%). In five cases with concomitant low‐grade adenomas, only one case showed LOH in low‐grade adenoma foci. In high‐grade dysplasia with/without submucosal invasion, early and homogeneous LOH of one to several chromosomal arms was detected. Overall, homogeneous and thus early LOH were most frequently detected on 17p (seven of 10 cases with 17p LOH), followed by 3p (two of three cases with 3p LOH), and 5q (four of seven cases with 5q LOH). In addition to homogeneous LOH, the LOH patterns observed in different portions of dysplasias and invasive cancers in individual cases identified several different genetic patterns of tumour progression, either with linear or branching (divergent) trees. Positive immunostaining for p53 was detected in 10 of the 13 cases; of these, five cases were concomitant with 17p LOH in all of the microdissected foci, four cases were concomitant with 17p LOH in a majority of foci and, one case showed retention of 17p. Except for the flat configuration and early 17p LOH, genetic heterogeneity in the flat high‐grade dysplastic foci was found to be similar to genetic chaos in the late dysplastic and preinvasive stages of exophytic adenoma. These findings suggest a potentially aggressive course for these neoplasms. Copyright © 2002 John Wiley & Sons, Ltd.
Significance of loss of heterozygosity of the RB1 gene during tumour progression in well‐differentiated liposarcomas
Authors: Schneider‐Stock Regine , Boltze Carsten , Jaeger Viola , Stumm Marcus , Seiler Christiane , Rys Janusz , Schütze Karin , Roessner Albert 
Published: October 2002

AbstractTumour progression can be investigated in liposarcomas showing a transition from a low‐grade well‐differentiated (WD) to a high‐grade dedifferentiated (DD) variant. As RB1 gene alterations are common defects in sarcomas, this study examined the frequency of RB1 loss of heterozygosity (LOH) in a group of 14 well‐differentiated liposarcomas (WDLs) and 17 well‐differentiated/dedifferentiated liposarcomas (WD/DDLs), using a microdissection approach (PALM laser pressure catapulting) that allows the two histological components to be separated for polymerase chain reaction (PCR) analysis. In addition, RB1 protein expression and the Mib1 proliferation index were determined by immunohistochemistry and interphase FISH was performed with an RB1 probe at 13q14. By the use of four intragenic polymorphic RB1 markers (introns 1, 17, 20, and 25) for PCR, allelic losses were found only in the DD parts, but never in the pure WDLs or in the WD components of the WD/DDLs investigated. Furthermore, DD areas characterized by a heterogeneous RB1 protein expression pattern (35–65% immunopositivity), as compared with 90–100% RB1 positivity in WD areas, showed a marked increase in Mib1 proliferation index (19.6% versus 1.8% in WD areas; p<0.001). Interphase fluorescence in situ hybridization (FISH) detected a higher RB1‐LOH rate in the DD components of WD/DDLs. Considering the different detection sensitivities of the three methodologies, it is concluded that loss of RB1 function already begins in the WDL, and that the tumour cell population with RB1‐LOH starts prevailing in the tumour mass during progression of a WDL. Copyright © 2002 John Wiley & Sons, Ltd.
Vascular endothelial growth factor (VEGF) is expressed by neoplastic Hodgkin–Reed–Sternberg cells in Hodgkin's disease
Authors: Doussis‐Anagnostopoulou Ipatia A. , Talks Kate L. , Turley Helen , Debnam Paul , Tan Daphne C. , Mariatos George , Gorgoulis Vassilis , Kittas Christos , Gatter Kevin C. 
Published: October 2002

AbstractVascular endothelial growth factor (VEGF) is involved in tumour angiogenesis, an important process for the growth and metastatic potential of solid tumours. Numerous studies have demonstrated up‐regulation of VEGF at both mRNA and protein level in various tumours and a correlation with advanced stage and prognosis has been demonstrated in some cases. Limited information exists about its role in lymphoid malignancies and in particular, Hodgkin's disease. The present study examined the immunohistochemical expression of VEGF using the monoclonal antibody VG1 in a series of 61 cases of Hodgkin's disease, including both classical Hodgkin's disease and the nodular lymphocyte predominance variant, and correlated these results with microvessel density, using an anti‐CD31 monoclonal antibody. In 41 cases (70.6%) of classical Hodgkin's disease and one of the three cases of nodular lymphocyte predominance Hodgkin's disease, the neoplastic Reed–Sternberg and Hodgkin cells expressed VEGF. The staining observed was cytoplasmic, either diffuse or with a focal paranuclear distribution. Macrophages were always positive, while reactive lymphocytes showed occasional positivity. A variable amount of strong extracellular staining was also observed in the tissue stroma and intravascular plasma staining was prominent. There was no statistically significant relationship between VEGF expression and the subtype of Hodgkin's disease or microvessel density. In vitro studies using the Reed–Sternberg cell lines L428 and KM‐H2 were also performed in both normoxia and hypoxia and VEGF protein production was assessed by flow cytometry (FACS), immunoassay of cell culture supernatant, and RT‐PCR. Analysis by FACS demonstrated a subset of cells in both cell lines reacting with VG1 and analysis of secreted VEGF (pg/ml per 1×106 cells) in cell culture supernatant confirmed the normoxic production in both cell lines and significant hypoxic induction (p<0.005). Additionally, both cell lines expressed VEGF mRNA, as demonstrated using the RT‐PCR method. In conclusion, neoplastic cells express VEGF in Hodgkin's disease, as is the case in solid tumours, and this expression may be induced by hypoxia. The presence of VEGF in reactive macrophages and in the extracellular matrix might facilitate tumour progression. Copyright © 2002 John Wiley & Sons, Ltd.
Cardiac stem cells
Authors: Hughes Siân 
Published: October 2002

AbstractAugmentation of myocardial performance in experimental models of therapeutic infarction and heart failure has been achieved by the transplantation of exogenous cells into damaged myocardium, a procedure known as cellular cardiomyoplasty (CCM). Historically, a wide range of cell types have been used for CCM, including rat and human fetal ventricular myocytes, but the availability of human fetal donor cells for clinical purposes is limited. The quest for suitable alternative donor cells has prompted research into the use of both embryonic stem (ES) cells and adult somatic stem cells, but the optimal choice of donor cell source is not yet known. Recently, there has been a growing body of evidence that multipotent somatic stem cells in adult bone marrow exhibit tremendous functional plasticity and can reprogramme in a new environmental tissue niche to give rise to cell lineages specific for the new organ site. This phenomenon has made a huge impact on myocardial biology and has captured the imagination of scientists who have recently discovered that multipotent adult bone marrow haematopoeitic stem cells and mesenchymal stem cells can repopulate infarcted rodent myocardium and differentiate into both cardiomyocytes and new blood vessels. These data, coupled with the identification of a putative primitive cardiac stem cell population in the adult human heart, may pave the way for novel therapeutic modalities for enhancing myocardial performance and treating end‐stage cardiac disease. Copyright © 2002 John Wiley & Sons, Ltd.
Distinct promoter hypermethylation of p16INK4a, CDH1, and RAR‐beta in intestinal, diffuse–adherent, and diffuse–scattered type gastric carcinomas
Authors: Oue Naohide , Motoshita Junichi , Yokozaki Hiroshi , Hayashi Ken , Tahara Eiichi , Taniyama Kiyomi , Matsusaki Keisuke , Yasui Wataru 
Published: October 2002

AbstractHypermethylation of CpG islands in gene promoters is associated with silencing of various tumour suppressor genes. Recent studies of colorectal and gastric carcinomas have defined a CpG island methylator phenotype (CIMP), which involves the targeting of multiple genes by promoter hypermethylation. In this study, methylation‐specific polymerase chain reaction (PCR) was performed to study methylation of CpG islands in the promoters of the p16INK4a, cadherin 1 (CDH1), and retinoic acid receptor‐beta (RAR‐beta) genes in 45 gastric carcinomas and to investigate whether CDH1 and RAR‐beta promoter hypermethylation is associated with CIMP‐positive gastric carcinoma. CpG island hypermethylation of the p16INK4a, CDH1, and RAR‐beta promoters was detected in 12 (27%), 26 (58%), and 24 (53%) of the 45 gastric carcinomas, respectively. Hypermethylation of the p16INK4a promoter was more common in intestinal type than in diffuse type gastric carcinomas (p = 0.0023; Fisher's exact test) and was inversely associated with p53 mutations (p = 0.0225; Fisher's exact test). However, CDH1 and RAR‐beta promoter hypermethylation was observed more frequently in diffuse–scattered type gastric carcinoma than in other types (intestinal and diffuse–adherent types) (p = 0.0175 and p = 0.0335, respectively; Fisher's exact test) and was not associated with p53 mutation status. Moreover, hypermethylation of the CDH1 and RAR‐beta promoters occurred concordantly (p < 0.0001; Fisher's exact test). These results suggest that at least two types of promoter methylation status are involved in the development of the intestinal (p16INK4a promoter hypermethylation) and diffuse–scattered types (CDH1 and RAR‐beta promoter hypermethylation) of gastric carcinoma. Copyright © 2002 John Wiley & Sons, Ltd.
Loss of heterozygosity for the NF2 gene in retinal and optic nerve lesions of patients with neurofibromatosis 2
Authors: Chan Chi‐Chao , Koch Christian A. , Kaiser‐Kupfer Muriel I. , Parry Dilys M. , Gutmann David H. , Zhuang Zhengping , Vortmeyer Alexander O. 
Published: October 2002

AbstractIndividuals affected with the neurofibromatosis 2 (NF2) cancer predisposition syndrome develop specific ocular lesions. To determine whether these lesions result from altered NF2 gene expression, microdissection and PCR were used to investigate 40 ocular lesions from seven eyes of four NF2 patients for LOH, with markers that flank the NF2 gene on chromosome 22q. NF2 protein (merlin) expression was also evaluated in these lesions, using immunohistochemistry. Retinal hamartoma was observed in all seven eyes, including one with combined pigment epithelial and retinal hamartoma (CPERH). Retinal tufts were present in four eyes (three patients), retinal dysplasia in two eyes (two patients), optic nerve neurofibroma in one eye, iris naevoid hyperplasia in two eyes (two patients) and pseudophakia in all eyes. Markers were informative in three patients (six eyes from three unrelated families). One patient was non‐informative due to prolonged decalcification. All retinal and optic nerve, but not iris lesions, demonstrated consistent LOH for the NF2 gene. Merlin was not expressed in the retina, optic nerve, or iris lesions. These results suggest that inactivation of the NF2 gene is associated with the formation of a variety of retinal and optic nerve lesions in NF2 patients. Copyright © 2002 John Wiley & Sons, Ltd.