J R Vielkind

University of British Columbia - Vancouver, Vancouver, British Columbia, Canada

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Publications (31)106.16 Total impact

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    ABSTRACT: Neurofibromatosis 1 (NF1) is an autosomal dominant disease that predisposes individuals to developing benign neurofibromas. Some features and consequences of NF1 appear to result from partial deficiency of neurofibromin (Nfn), the NF1 gene protein product, as a result of haploinsufficiency for the NF1 gene. Other features and consequences of NF1 appear to involve total deficiency of Nfn, which arises as a result of either loss of function of the second NF1 allele or excess degradation of Nfn produced by the second allele in a particular clone of cells. We used immunofluorescence to assess the presence of Nfn in putative Schwann cells (S100B(+) ) and non-Schwann cells (S100B(-) ) in 36 NF1-derived benign neurofibromas classified histologically as diffuse or encapsulated. The S100B(+) /Nfn(-) cell population made up only 18% ± 10% (mean ± standard deviation) of the neurofibroma cells in both the diffuse and encapsulated neurofibromas. The proportion of S100B(+) /Nfn(+) cells was significantly higher and the proportion of S100B(-) /Nfn(-) cells was significantly lower in diffuse neurofibromas than in encapsulated neurofibromas. We isolated S100B(+) /Nfn(+) , S100B(+) /Nfn(-) , and S100B(-) /Nfn(+) cells by laser microdissection and, using X-chromosome inactivation profiles, assessed clonality for each cell type. We showed that, although some neurofibromas include a subpopulation of S100B(+) /Nfn(-) cells consistent with clonal expansion of a Schwann cell progenitor that has lost function of both NF1 alleles, other neurofibromas do not show evidence of monoclonal proliferation of Schwann cells. Our findings suggest that, although clonal loss of neurofibromin function is probably involved in the development of some NF1-associated neurofibromas, other pathogenic processes also occur.
    Journal of Neuroscience Research 06/2011; 89(9):1451-60. · 2.97 Impact Factor
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    ABSTRACT: Multiple neurofibromas are cardinal features of neurofibromatosis 1 (NF1). Several different types of NF1-associated neurofibromas occur, each distinct in terms of pathological details, clinical presentation, and natural history. Mast cells are present in most neurofibromas and have been shown to be critical to the origin and progression of neurofibromas in both human NF1 and relevant mouse models. In this investigation, the authors determined whether mast cell involvement is the same for all types of NF1-associated neurofibromas. They examined the density and distribution of mast cells within 49 NF1-associated neurofibromas classified histopathologically as diffuse or encapsulated on the basis of the presence or absence of the perineurium or its constituent cells. They made two observations: (1) Diffuse neurofibromas had significantly higher densities of mast cells than did encapsulated neurofibromas, and (2) mast cells were evenly distributed throughout diffuse neurofibromas but were primarily restricted to the periphery of encapsulated neurofibromas. The differences in mast cell density and distribution differentiate the two basic types of NF1-associated neurofibromas, suggesting that the pathogenesis of diffuse and encapsulated neurofibromas may be significantly different.
    Journal of Histochemistry and Cytochemistry 06/2011; 59(6):584-90. · 2.26 Impact Factor
  • Bahram Sadaghiani, Bruce J. Crawford, Juergen R. Vielkind
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    ABSTRACT: The changes in distribution of chondroitin sulfate proteoglycans (CSs) and fibronectin (FN), two major components of the extracellular matrix (ECM), are described during the development and migration of neural crest cells in two Xiphophorus species offish, X. helleri (swordtail) and X. maculatus (platyfish), using immunohistochemistry. A detailed description of the developmental changes in HNK-1-positive ECM components is also provided and compared with those of CSs and FN. HNK-1 antigen was also used as a marker for the neural crest cells. Weak staining for CSs, FN, and HNK-1-positive ECM was present in the neural crest cell migration pathways prior to migration of the cells. The level of staining increased dramatically during migration of these cells and decreased again after migration was nearly completed. Staining for CSs was more widespread than staining for FN, while the HNK-1 staining pattern was more clearly restricted to the migratory pathways than those seen with the other two antibodies. The correlation between the spatiotemporal relationship of these ECM components and the segregation and migration of neural crest cells suggests that these ECM molecules may be involved in both initiating and guiding the migration of neural crest cells in these fish. The HNK-1-positive ECM may play a more critical role than CSs and FN.
    Canadian Journal of Zoology 02/2011; 72(7):1340-1353. · 1.50 Impact Factor
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    B Sadaghiani, B J Crawford, J R Vielkind
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    ABSTRACT: Immunization of rats with gelatin-affinity column purified fibronectin (FN) from rainbow trout (Oncorhynchus mykiss) plasma produced a polyclonal antiserum that reacts specifically with FN in immunoblotted protein extracts and cultured cells, not only from trout but also from swordtails (Xiphophorus helleri). Most importantly, this antiserum specifically stains FN-containing structures in sections from embryos, as well as skin and dorsal fin of swordtails and platyfish (Xiphophorus maculatus), allowing, e.g., correlation of the distribution of FN with neural crest cell development in Xiphophorus. The antiserum also cross-reacts with FN in sections from embryos of the Japanese medaka (Oryzias latipes) and coho salmon (Oncorhynchus kisutch). In addition to the polyclonal antibodies, monoclonal anti-trout FN antibodies were produced in rats. These did not exhibit reactivity on sections, but stained the cultured fish cells and FN in immunoblots. Both types of antibodies may be of interest to the fish industry for marking the level of FN as an indicator, not only for infectious diseases, but also for certain developmental stages such as smoltification and spawning.
    Biochemistry and Cell Biology 01/2011; 72(7-8):343-8. · 2.92 Impact Factor
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    ABSTRACT: Expression of microRNA genes is profoundly altered in cancer but their role in the development of androgen-independent prostate cancer has received limited attention as yet. In this study, we report a functional impact in prostate cancer cells for overexpression of the microRNA miR-616, which occurred consistently in cells that were androgen-independent (AI) versus androgen-dependent (AD). miR-616 overexpression was confirmed in malignant prostate tissues as opposed to benign prostate specimens. Stable miR-616 overexpression in LNCaP cells by a lentiviral-based approach stimulated AI prostate cancer cell proliferation in vitro whereas concomitantly reducing androgen-induced cell growth. More importantly, miR-616 overexpressing LNCaP cells overcame castration resistance as shown by an enhanced ability to proliferate in vivo after bilateral orchiectomy. Conversely, antagonizing miR-616 in AI prostate cancer cells yielded opposite effects. Microarray profiling and bioinformatics analysis identified the tissue factor pathway inhibitor TFPI-2 mRNA as a candidate downstream target of miR-616. In support of this candidacy, we documented interactions between miR-616 and the 3'UTR of TFPI-2 and determined TFPI-2 expression to be inversely correlated to miR-616 in a series of prostate cell lines and clinical specimens. Notably, reexpression of TFPI-2 in LNCaP cells with stable miR-616 overexpression rescued the AD phenotype, as shown by a restoration of androgen dependence and cell growth inhibition. Taken together, our findings define a functional involvement for miR-616 and TFPI-2 in the development and maintenance of androgen-independent prostate cancer.
    Cancer Research 01/2011; 71(2):583-92. · 8.65 Impact Factor
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    ABSTRACT: Carcinoma of the prostate (CaP) is a serious health problem. The altered molecular mechanisms that lead to this disease are poorly understood. Specimens from radical prostatectomies and blood were collected from 18 CaP surgery patients. For CGH studies, 20 CaP-related samples (16 Gleason grade 3, 3 higher grades, 1 BPH sample) and 18 samples of patient-matched normal epithelial cells were obtained by laser-assisted microdissection from frozen sections of the 18 prostatectomy specimens. High resolution SMRT aCGH was used to compare genomic profiles of prostatic samples to patient-matched blood and pooled female DNA. TMPRSS2-ERG fusion transcript analysis was performed by RT-PCR in relation to alterations detected at the TMPRSS2 locus. Our comprehensive aCGH approach allowed us to define 35 regions of recurrent alterations while excluding germline copy number polymorphisms. Novel regions identified include 2q14.2, containing INHBB, and 17q21.31. The TMPRSS2 locus at 21q22.3 may be a hotspot for rearrangements with 75% of the alterations resulting in the expression of a TMPRSS2-ERG fusion transcript. Differences in fusion expression in different areas in an individual tumor focus and expression in adjacent normal epithelium supported intrafocal heterogeneity and field cancerization, respectively. Both features challenge our efforts to develop more objective markers for diagnosis and prediction of the severity of CaP. The high-density array enabled precise mapping of genomic alterations and consequently definition of minimum altered regions smaller than previously reported thus facilitating identification of those genes that contribute to the cancer transformation process.
    The Prostate 04/2009; 69(9):961-75. · 3.84 Impact Factor
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    ABSTRACT: Identification of genomic alterations associated with the progression of prostate cancer may facilitate the better understanding of the development of this highly variable disease. Matched normal, premalignant high-grade prostatic intraepithelial neoplasia and invasive prostate carcinoma cells were procured by laser capture microdissection (LCM) from human radical prostatectomy specimens. From these cells, comparative DNA fingerprints were generated by a modified PCR-based technique called scanning of microdissected archival lesion (SMAL)-PCR. Recurrent polymorphic fingerprint fragments were used in tagging altered chromosomal regions. Altered regions were found at cytobands 1p31.3, 1q44, 2p23.1, 3p26.3, 3q22.3, 4q22.3, 4q35.2, 5q23.2, 8q22.3, 8q24.13, 9q21.3, 9q22.32, 10q11.21, 11p13, 12p12.1, 13q12.1, 16q12.2 and 18q21.31. Candidate genes in the surrounding area that may possibly harbor mutations that change normal prostatic cells to progress into their tumor stages were proposed. Of these fragments, a 420 bp alteration, absent in all 26 normal samples screened, was observed in 2 tumors. This fragment was cloned, sequenced and localized to chromosome 12p12.1. Within this region, candidate gene sex determining region Y-box 5 (SOX5) was proposed. Further studies of SOX5 in cell lines, xenografts and human prostate specimens, at both the RNA and protein levels, found overexpression of the gene in tumors. This overexpression was then subsequently found by fluorescent in situ hybridization to be caused by amplification of the region. In conclusion, our results suggest LCM coupled with SMAL-PCR DNA fingerprinting is a useful method for the screening and identification of chromosomal regions and genes associated with cancer development. Further, overexpression of SOX5 is associated with prostate tumor progression and early development of distant metastasis.
    International Journal of Cancer 01/2009; 124(10):2323-32. · 6.20 Impact Factor
  • Bahram Sadaghiani, Juergen R. Vielkind
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    ABSTRACT: Neural tubes were explanted from the trunk of various embryonic stages of three teleost fish, Xiphophorus maculatus (platyfish), X. helleri (swordtail), and Oryzias latipes (Japanese medaka) with the aim to obtain in vitro differentiating neural crest cells. Outgrowth of cells was observed immediately after attachment of the explants on dishes coated with fibronectin. The outgrowing cells stained with the HNK-1 monoclonal antibody indicating that they were neural crest cells. Maximum cell outgrowth was obtained from explants of stage 9 of Xiphophorus and 19 of medaka, i.e., from stages characteristic of maximal neural crest cell segregation, and by the use of Leibovitz's (L-15) medium supplemented with 20% FBS. In this medium cells survived for more than two weeks; M199 also gave satisfactory results but DMEM allowed only poor cell growth and survival. Neuronal cells could be observed in all cultures after 48 hr, in some medaka cultures these cells were mixed with pigment cells but homogeneous pigment cell cultures were also observed. This in vitro system will be invaluable for the study of the developmental potential of fish neural crest cells and the contributions of extrinsic factors in neural crest cell fate.
    Embryologia 07/2008; 32(5):513 - 520. · 2.21 Impact Factor
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    ABSTRACT: Growth differentiation factor (GDF15) is a distant member of the transforming growth factor-beta superfamily, a diverse group of structurally related proteins that exert multiple effects on cell fate such as on cell growth and differentiation but little is known about GDF15 in these processes. Previously we observed the mature GDF15 to be associated with human prostate carcinogenesis hence prompting us to study GDF15 further. Here we report gdf15 expression both at the RNA and protein levels, in normal prostatic tissues of wild type (wt) and prostatic intraepithelial neoplasia (PIN) of transgenic (Tg) 12T-7s model mice during embryonic, postnatal, and adult prostate formation up to 15 weeks after birth. Dynamic changes in expression, at both the mRNA and protein level, correlated with cell proliferation and differentiation during distinct phases of normal mouse prostate development and alterations in the dynamics of gdf15 expression correlated with the changes in development resulting in PIN formation. Most notably mature gdf15 protein was significantly elevated during hyperplasia and PIN development. Changes in the protein levels did not always correlate well with the mRNA levels. This was more prominent during PIN than during normal prostate development suggesting that this may also be an indicator of disturbed regulation of gdf15 in PIN. We propose that gdf15 is a growth factor with dual function either promoting proliferation or growth arrest and differentiation due most likely to differences in cellular differentiation. Because of the differentiation defect in PIN its epithelium no longer responds to gdf15 by cellular growth arrest as does the normal epithelium and gdf may even stimulate proliferation. The data supports our hypothesis that GDF15 plays a role in the early stages of human prostate cancer.
    Differentiation 05/2007; 75(4):325-36. · 2.86 Impact Factor
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    ABSTRACT: LIM domain only 2 (LMO2) proteins are important regulators in determining cell fate and controlling cell growth and differentiation. This study has investigated LMO2 expression in human prostatic tissue specimens, prostate cancer cell lines, and xenografts; and has assessed the possible role and mechanism of LMO2 in prostate carcinogenesis. Immunohistochemical analysis on a tissue microarray consisting of 91 human prostate specimens, including normal, prostatic hyperplasia, high-grade prostatic intraepithelial neoplasia, and invasive carcinoma, revealed that overexpression of LMO2 was significantly associated with advanced tumour stage, as measured by Gleason score (p = 0.012), as well as with the development of distant metastasis (p = 0.018). These data were supported by quantitative real-time PCR experiments, where LMO2 mRNA levels were found to be significantly higher in prostate tumour specimen than in normal epithelium (p = 0.037). The expression of LMO2 in cell lines and xenografts representing androgen-dependent (AD) and androgen-independent (AI) prostate cancer stages was further studied. Consistent with the in vivo data, LMO2 mRNA and protein were found to be overexpressed in the more aggressive AI cells (PC3, DU145, and AI CWR22 xenografts) compared with less aggressive AD cells (LNCaP and AD CWR22 xenografts). Furthermore, stable introduction of LMO2 into LNCaP cells conferred enhanced cell motility and invasiveness in vitro, accompanied by down-regulation of E-cadherin expression. Taken together, these findings provide the first evidence to support the hypothesis that LMO2 may play an important role in prostate cancer progression, possibly via repression of E-cadherin expression.
    The Journal of Pathology 03/2007; 211(3):278-85. · 7.59 Impact Factor
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    ABSTRACT: There is great interest in the sex chromosomes of Xiphophorus fishes because both WY/YY and XX/XY sex-determining mechanisms function in these species, with at least one taxon possessing all three types of sex chromosomes, and because in certain interspecific hybrids melanoma arises as a consequence of inheritance of the sex-linked macromelanophore determining locus (MDL). Representational difference analysis (RDA) has been used to clone two sequences from the sex-determining region of X. maculatus, including a cholinergic receptor, nicotinic, delta polypeptide (CHRND) orthologue. Allele-specific assays for these sequences, as well as for the sex-linked XMRK1 and XMRK2 genes, were developed to distinguish W, X, and Y chromosomes derived from a X. maculatus (XX/XY) strain and a X. helleri (WY/YY) strain. Linkage mapping localized these markers to linkage group (LG) 24. No recombinants were observed between XMRK2 and MDL, confirming a role for XMRK2 in macromelanophore development. Although the master sex-determining (SD) locus certainly resides on Xiphophorus LG 24, autosomal loci are probably involved in sex determination as well, as indicated by the abnormal sex ratios in the backcross hybrids that contrast theoretical predictions based on LG 24 genotyping. Marker development and allelic discrimination on the Xiphophorus sex chromosomes should prove highly useful for studies that utilize this genus as an animal model.
    Zebrafish 02/2006; 3(1):23-37. · 2.88 Impact Factor
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    ABSTRACT: Identification of proteomic alterations associated with early stages in the development of prostate cancer may facilitate understanding of progression of this highly variable disease. Matched normal, high-grade prostatic intraepithelial neoplasia (hPIN) and prostate cancer cells of predominantly Gleason grade 3 were procured by laser capture microdissection from serial sections obtained from snap-frozen samples dissected from 22 radical prostatectomy specimens. From these cells, protein profiles were generated by surface-enhanced laser desorption/ionization-time of flight mass spectrometry. A 24-kDa peak was observed at low or high intensity in profiles of prostate cancer cells in 19 of 27 lesions and at low intensity in 3 of 8 hPIN lesions but was not detectable in matched normal cells. SDS-PAGE analysis of prostate cancer and matched normal epithelium confirmed expression of a prostate cancer-specific 24-kDa protein. Mass spectrometry and protein data-based analysis identified the protein as the dimeric form of mature growth differentiation factor 15 (GDF15). The increased expression of mature GDF15 protein in prostate cancer cells cannot be explained on the basis of up-regulation of GDF15 mRNA because reverse transcription-PCR analysis showed similar amounts of transcript in normal, hPIN, and prostate cancer cells that were obtained by laser capture microdissection in the same set of serial sections from which the protein profiles were obtained. Our findings suggest that early prostate carcinogenesis is associated with expression of mature GDF15 protein.
    Cancer Research 10/2004; 64(17):5929-33. · 8.65 Impact Factor
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    Wan L. Lam, Juergen R. Vielkind
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    ABSTRACT: Early detection and intervention are key to a favorable prognosis in prostate cancer. Despite advances in the detection and treatment of prostate cancer, the mortality rate remains high. To improve survival, early detection and treatment strategies tailored to pre-invasive prostate cancer are required. The authors propose to catalog genetic alterations associated with the developmental stages of disease for use as diagnostic tools, and to identify the critical genes that drive the transformation of premalignant lesions to tumors for use as molecular targets for novel treatment design. The combination of laser capture microdissection (efficient isolation of specific cell types from hundreds of specimens) and SMAL DNA fingerprinting technology (high-throughput analysis of genomic targets using minute quantities of DNA yielded from the microdissected cells) will facilitate systematic comparison of samples in various stages of disease development. By the end of this work, the authors will have identified a set of genetic loci (and genes) by virtue of their frequency of alteration in premalignant lesions and subsequently in low-grade tumors. They will have established a publicly accessible "genetic alterations in prostate cancer" database that catalogs somatic changes present in the various stages of cancer progression. This information will contribute to the fundamental understanding of prostate cancer pathogenesis.
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    ABSTRACT: Hybrids between distinct Xiphophorus species have been utilized for over 70 years to study melanoma and other neoplasms that can develop spontaneously in hybrid offspring. Genetic linkage mapping has proven to be important in delineating genomic areas that harbor oncogenes and tumor suppressors. Within this report, two parallel backcrosses have been utilized to generate a genetic linkage map for Xiphophorus fishes. Isozyme/allozyme, RFLP and PCR-based mapping techniques, including AP-PCR/RAPDs and microsatellite loci were utilized. The derived linkage map provides a total of 403 mapped polymorphisms distributed among 24 linkage groups, representative of 24 acro- and telocentric chromosome pairs. Genomic coverage is approximately one marker per 5.8 cM. Detailed genotypic analysis of the utilized hybrids revealed two areas of the genome that show significant segregation distortion. Loci within the linkage group harboring the sex determining locus (LG 24) and an autosomal linkage group (LG 21) show highly significant deviations from Mendelian expectations. This phenomenon is not present in a hybrid cross that utilizes a different backcross hybrid progenitor species. The derived map with sequence-tagged markers provides a framework for physical map generation, large-scale genomic sequencing and will further enable cross-genome comparisons of vertebrate genomes.
    Zebrafish 02/2004; 1(3):287-304. · 2.88 Impact Factor
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    ABSTRACT: We have cloned, sequenced, and characterized the RNA expression properties of a fish CDKN2 gene from Xiphophorus helleri and X. maculatus. This gene, termed CDKN2X, shows a high degree of amino acid sequence similarity to members of the mammalian CDKN2 gene family, which includes the tumor suppressor loci CDKN2A (P16) and CDKN2B (P15). Comparative sequence analysis suggests that fish CDKN2X is similarly related to all four mammalian gene family members, and may represent a descendant of an ancestral prototypic CDKN2 gene. CDKN2X was mapped to a region on autosomal Xiphophorus linkage group V (LG V) known to contain the DIFF gene that acts as a tumor suppressor of melanoma formation in X. helleri/X. maculatus backcross hybrids. Thus, CDKN2X may be a candidate for the tumor suppressor DIFF gene. Here we have sequenced CDKN2X in both Xiphophorus species and have characterized its expression in normal and melanotic tissues within control and backcross hybrid fish. A simultaneous expressional analysis of the Xmrk-2 tyrosine kinase receptor gene, which is strongly implicated in melanomagenesis in this system, was also performed. RT - PCR analyses revealed that both genes were highly expressed in melanomas. For CDKN2X, this result contrasts numerous findings in human tumors including human melanoma in which either CDKN2A (P16) deactivation or LOH was observed.
    Oncogene 10/1999; 18(36):5088-99. · 7.36 Impact Factor
  • J R Vielkind, K Huhn, V A Tron
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    ABSTRACT: XMEL is a monoclonal antibody raised against part of the extracellular domain of the putative tyrosine kinase receptor protein implicated in the pathogenesis of melanoma formation in the Xiphophorus fish melanoma model. Our objective in this study was to determine the diagnostic and prognostic utility of XMEL for human melanoma. Formalin-fixed tissue from 82 melanomas, 42 carcinomas, 23 neural tumors, 12 lymphomas and 12 sarcomas were immunostained with XMEL and compared with a widely used melanoma antibody, HMB-45. The sensitivity of HMB-45 (83.1%) was similar to that of XMEL (79.8%). XMEL detected 7 melanomas that were HMB-45 negative. Specificity for detection of melanoma was greater with HMB-45 (95.5%) as compared to XMEL (80.9%). Of interest, all 4 prostatic adenocarcinomas were XMEL positive. These data suggest that XMEL is as sensitive but not as specific as HMB-45 in the detection of cutaneous melanoma but may serve as an ancillary antibody to improve diagnostic yield. The consistent positivity of XMEL in melanoma lends support to the hypothesis that the detected protein plays a role in melanoma pathogenesis. XMEL reactivity is not an independent prognosticator of death from melanoma in 37 melanomas from patients with at least 10 years' follow-up. These data and the fact that XMEL shows variable reactivity with metastatic melanomas but almost 100% reactivity with the primary melanomas suggest that the antigen recognized by the XMEL antibody may be important in the early stages of melanoma progression. This is supported by our earlier observation that XMEL is reactive with dysplastic nevi, a precursor of malignant melanoma.
    Journal of Cutaneous Pathology 12/1997; 24(10):620-7. · 1.77 Impact Factor
  • V A Tron, R Crawford, J R Vielkind
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    ABSTRACT: We have previously shown that a novel monoclonal antibody, XMEL, exhibited reactivity with deep primary melanomas while showing no reactivity with other tumours and normal tissue. XMEL was raised against a part of the extracellular domain of Xmrk, a growth factor receptor presumed to mediate melanoma formation in the Xiphophorus fish model. Here we investigate the range of XMEL immunohistochemical reactivity in paraffin sections from human common acquired and dysplastic naevi of both junctional and compound type. The strongest reactivity was observed with the compound dysplastic naevi. We conclude that the antigen recognized by XMEL acts early in the cascade of genetic alterations underlying progression into malignant melanoma. Our results also support the notion that the dysplastic naevus may play a role in progression of human malignant melanoma and may indeed represent the precursor stage.
    Melanoma Research 07/1997; 7(3):209-13. · 2.52 Impact Factor
  • B. W. Woolcock, B. M. Schmidt, J. R. Vielkind
    Journal of Dermatological Science 01/1996; 12(1):88-88. · 3.52 Impact Factor
  • Journal of Dermatological Science 01/1996; 12(1):83-83. · 3.52 Impact Factor
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    ABSTRACT: Pigment (macromelanophore) patterns in the platyfish Xiphophorus maculatus are due to a complex pigmentary locus; for example, the spotted-dorsal (Sd) fin pattern is due to the Sd locus. In interspecific backcross hybrids with the swordtail X. helleri, the Sd pattern changes into benign or malignant dorsal fin melanoma as a result of hemi- or homozygous loss of a platyfish regulatory (R) gene, the tumor suppressor gene Diff, that appears to play a role in the final differentiation of macromelanophores. Closely linked to the pigmentary locus is an epidermal growth factor receptor-like gene, Xmrk-2, that has arisen by duplication from the linked Xmrk-1. The transcriptional expression of the Xmrk genes was determined in various tissues including Sd pigment patterns and melanomas of various growth potential using reverse transcription-polymerase chain reaction. While Xmrk-1 expression was found in all tissues examined, Xmrk-2 expression correlated with pigment cell growth. Xmrk-2 was highly expressed in the dorsal fin exhibiting the Sd pattern but drastically reduced in a platyfish mutant which has lost the capacity to form these pigment cells in the dorsal fin. Most interestingly, Xmrk-2 expression increased with the proliferative capacity of the melanomas but declined once melanoma growth ceased. We conclude that Xmrk-2 plays a role in the formation of the pigment pattern cell type, perhaps in proliferation of precursor cells, which, in melanoma, are kept in a proliferative state due to loss of Diff.(ABSTRACT TRUNCATED AT 250 WORDS)
    Cell growth & differentiation: the molecular biology journal of the American Association for Cancer Research 07/1994; 5(6):575-83.

Publication Stats

409 Citations
106.16 Total Impact Points

Institutions

  • 1990–2011
    • University of British Columbia - Vancouver
      • • Department of Pathology and Laboratory Medicine
      • • Cell and Developmental Biology (CELL)
      • • Division of Endocrinology
      Vancouver, British Columbia, Canada
  • 1989–2011
    • BC Cancer Research Centre
      Vancouver, British Columbia, Canada