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Results for “molecular profiling”

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PubMed2002

Laser capture microdissection and microarray expression analysis of lung adenocarcinoma reveals tobacco smoking- and prognosis-related molecular profiles.

Recent expression profile analyses revealed that lung adenocarcinomas can be divided into several subgroups with diverse pathological features. Because cellular heterogeneity of tumors can confound these analyses, we used laser capture microdissection and microarray expression analysis to characterize the molecular profiles of lung adenocarcinomas. We found 45 genes delineating smokers and nonsmokers that were located at chromosomal loci frequently altered in non-small cell lung cancers, and 27 genes, which were differentially expressed between survivors and nonsurvivors 5 years after surgery. These results are consistent with the hypothesis that the abnormal expression of genes involved in maintaining the mitotic spindle checkpoint and genomic stability, e.g., hBUB3, hZW10, and APC2, contribute to the molecular pathogenesis and tumor progression of tobacco smoke-induced adenocarcinoma of the lung.

Adenocarcinoma↗

PubMed2004

Fractionation of Aloe vera L. inner gel, purification and molecular profiling of activity.

Products derived from the inner gel of the Aloe vera L. plant have demonstrated multiple clinical activities, and are used routinely to accelerate wound healing. However, typical of natural products, the complex nature of Aloe vera gels may contribute to diverse pharmacologic activities. Our focus on the hematopoietic activities of Aloe vera extracts is extended by these functional studies, which used purified fractions from Aloe vera gel and included a preliminary organ-specific in vitro molecular profile. Studies using a >99% pure carbohydrate fraction from Aloe vera extracts revealed increased hematopoietic and hematologic activity compared to the starting material. In addition, this fraction differentially regulated liver and lung cytokine mRNA levels, resulting in significant increases in message for hematopoietic cytokines [granulocyte colony stimulating factor (G-CSF) and stem cell factor (SCF)]. This profile of activity differed from another fraction obtained from Aloe vera, suggesting the potential for diverse pharmacologic activity. The molecular studies were undertaken using co-cultures of organ slices to limit the amount of purified material required. In summary, these studies revealed significant hematopoietic activity by both pharmacologic and molecular analysis using a >99% pure carbohydrate fraction from Aloe vera gels.

Aloe↗

PubMed2005

Properties of growth and molecular profiles of rat progenitor cells from ciliary epithelium.

Recent studies have demonstrated that multipotent retinal stem or progenitor cells can be isolated from the ciliary epithelium (CE) of the eye using a neurosphere culture. In this study, we investigated the properties of growth and differentiation, and molecular profiles of rat adult ciliary epithelium (CE)-derived retinal progenitors and forebrain (FB) derived neurospheres. Under clonogenic culture conditions, we found that the CE-derived neurospheres contained fewer undifferentiated cells compared with the FB-derived neurospheres, and that CE-derived neurospheres initially expressed the set of Notch pathway molecules genes including Notch 1 and Delta 1, HES-1 and HES-5, but partially lose their expression after passaging. Furthermore, we found that the CE-derived neurospheres did not express several markers for in vivo embryonic retinal progenitors. Additionally, when the eye was divided into four subregions along its dorsoventral and nasotemporal axes and progenitor cells were obtained from the subregions, the progenitor cells did not express the subregion specific transcription factors, suggesting that subregional specificity is not maintained in vitro. Together, our results demonstrate that CE-derived progenitor cells may have intrinsic limitations in the production of cell types.

Animals↗

PubMed1997

Molecular profile of Epstein-Barr virus in human immunodeficiency virus type 1-related lymphadenopathies and lymphomas.

Human immunodeficiency virus type 1 (HIV-1)-infected patients develop a spectrum of lymphoproliferative disorders ranging from nonneoplastic lymphadenopathies to B-cell lymphomas. Although evidence suggests that Epstein-Barr virus (EBV) might be involved, its molecular profile and expression pattern in HIV-1-related lymphoproliferations remain to be defined. Using polymerase chain reaction-based techniques, we studied EBV types and variants in 28 lymphadenopathy lesions and in 20 lymphomas (15 large cell and 5 Burkitt-like). EBV was detected in 89% of lymphadenopathies and in 80% of lymphomas; viral DNA content was significantly higher in the latter. EBNA2 and LMP1 gene analysis indicated that half of the EBV+ lymphadenopathies were coinfected with both EBV type 1 and 2 strains and/or multiple type 1 variants. Conversely, all but one lymphoma carried a single viral variant, consistently type 1 in large cell lymphomas, and type 2 in Burkitt-like tumors. Most lymphomas, but no lymphadenopathies, showed monoclonal Ig heavy-chain rearrangement. Analysis of 5 large cell lymphomas and 9 lymphadenopathies for EBV transcripts identified LMP1 mRNA in most samples, and the EBNA2 transcript in all tumors. These findings provide evidence of a heterogeneous EBV population in lymphadenopathy lesions, strengthen the notion that lymphomas arise from clonal expansion of EBV+ cells, and suggest different roles for EBV types 1 and 2 in HIV-1-related lymphoproliferations.

AIDS-Related Opportunistic Infections↗

PubMed2006

Biliary tract cancers: molecular profiling as a tool for treatment decisions. A literature review.

Biliary tract cancer is a quite rare disease; despite recent significant advances in imaging modalities, most of the patients have advanced disease at presentation thus making radical surgery not feasible. Many different chemotherapeutic regimens have been investigated in small uncontrolled studies, with generally disappointing results. We extensively reviewed the literature on this topic trying to give an explanation to chemoresistance in this setting of patients and considering the molecular profiling as a tool for treatment decision. This review is divided in two parts, in the first one we illustrated chemotherapy results and possible mechanisms of resistance. In the second part we analysed the new molecular targets developing an hypothesis about the future therapeutics perspectives.

Antineoplastic Agents↗

PubMed2002

Tissue microarray molecular profiling of early, node-negative adenocarcinoma of the rectum: a comprehensive analysis.

PURPOSE: Early-stage adenocarcinoma of the rectum treated with curative intent has a favorable overall prognosis; however, 20%-30% of the patients recur, and the majority ultimately die of disease. Recurrence and tumor-related mortality may be attributable to molecular abnormalities in primary tumors accounting for their more aggressive biological behavior. This study evaluates such molecular phenotypes with regard to cell cycle regulation and proliferation and determines their significance for patient outcome. EXPERIMENTAL DESIGN: One hundred patients with primary T(2-3), N(0) adenocarcinoma of the rectum uniformly treated by surgery alone were studied. Core biopsies of pathological specimens were assembled on tissue microarrays, and expression of p53, mdm-2, p21, Bcl-2, p27, cyclin D1, and Ki-67 was analyzed by immunohistochemistry. Molecular profiles were correlated with disease-free (DFS) and disease-specific survival (DSS). RESULTS: Despite previously described prognostic relevance of some of the investigated molecules in analyses where different stages of colorectal cancer were included, none of the cell cycle-regulatory or proliferation-related markers was associated with recurrence or survival. However, patients with tumors demonstrating down-regulation of p27, a cyclin-dependent kinase inhibitor and tumor suppressor gene associated with development of metastases, showed a trend toward reduced DFS and DSS (P = 0.06 and P = 0.07, respectively). CONCLUSIONS: In this homogeneous group of patients with early-stage, node-negative adenocarcinoma of the rectum uniformly treated by surgery alone, the investigated cell cycle-regulatory and proliferation-associated proteins appear to have no prognostic significance. However, down-regulation of p27 appears to be associated with a trend toward reduced DFS and DSS, which suggests further investigation of other p27-related pathways potentially relevant for metastatic disease.

Adenocarcinoma↗

PubMed2005

[Analysis of molecular profiles among Trypanozoon species and subspecies by MGE-PCR method].

OBJECTIVE: To analyze the relationship between genetic variability and evolution among Trypanosoma brucei (including T. b. brucei, T. b. rhodesiense and T. b. gambiense), T. evansi and T. equiperdum isolates. METHODS: Genomic DNAs of 26 trypanosome isolates were amplified by a mobile genetic elements (MGE) -PCR technique and cluster analysis was performed based on the molecular profiles with Neighbor-Joining method. RESULTS: The genetic variability among trypanosome isolates examined was obvious with an average genetic distance of 41.2% (ranged from 0 to 100%). Similarity coefficient among T. brucei isolates was 41.15% which was lower than that between T. evansi and T. equiperdum isolates. The closest relationship was found between T. evansi and T. brucei isolates with a similarity coefficient of 62.94%. The genetic variability between T. b. rhodesiense and T. b. brucei isolates was higher than that among T. b. gambiense isolates. CONCLUSION: Species and subspecies in Trypanozoon displayed a higher genetic variability; T. equiperdum isolates collected from China and from South America, and T. evansi isolates from China and from South America, should have a similar origin.

Animals↗

PubMed2004

Correlations between molecular profile and radiologic pattern in oligodendroglial tumors.

OBJECTIVE: To investigate possible correlations between tumor location and genetic alterations in a series of oligodendrogliomas. METHODS: A series of 158 consecutive oligodendrogliomas were retrospectively reviewed. In each case, the radiologic picture and the chromosome 1p (chr 1p) status of the tumor detected by the loss of heterozygosity technique were analyzed. Correlation between tumor location and molecular profile was made by chi2 tests. RESULTS: Eighty-eight of the 158 patients had low-grade oligodendrogliomas, and 70 had anaplastic oligodendrogliomas. Overall, oligodendrogliomas with chr 1p loss were located preferentially in the anterior part of the brain, whereas tumors with intact chr 1p affected mainly the posterior part of the brain (p = 0.0038). In terms of lobar involvement, a preferential location of oligodendrogliomas with chr 1p loss was found in the frontal lobes as compared with the temporal, parietal, and occipital tumors (p < 0.01). CONCLUSION: There is a significant correlation between loss of heterozygosity on chromosome 1p and tumor location in oligodendrogliomas, suggesting that subtypes of oligodendrogliomas could derive from site-specific precursors.

Adult↗

PubMed1998

Molecular profiling of tyrosine kinases in normal and cancer cells.

As the post-genome era is approaching, with vast amount of sequence information available and new technology developed, scientists are presented with opportunities to explore in simple analysis the structure and expression pattern of not just a single gene, but of an entire family of genes, if not the entire genome. The concept of 'molecular profiling' or 'expression array' has thus emerged. The need to simultaneously 'see' all genes in the same family is obvious under the precept of the combinatorial process being an underlying principle of complex biological systems: no gene exists in isolation, for virtually every molecule participates in intermolecular interactions. The activation of receptor tyrosine kinases through homo or hetero-dimerization is the prototypic example. In this review, a tyrosine kinase profile technique and its application to studying the expression of tyrosine kinases and the identification of novel kinases will be discussed. This serves as an introduction to the several interesting papers published in this special 'kinase' issue of the Journal of Biomedical Sciences, using this technique. A new simplified approach, kinase display, which is an extension of the profiling method and requires only restriction digestion and gel analysis will also be introduced.

Gene Expression↗

PubMed2001

Molecular profiling of tissue samples using laser capture microdissection.

The management of cancer and other genetically based diseases is far from optimal in even our most advanced medical centers. There is still uncertainty regarding how diseases will progress in certain patients, toxicity that must be tolerated with imprecise treatment regimens and significant potential for treatment failure. As our understanding of the complexity of these diseases has increased, it has become clear that we must move toward precisely tailored approaches to treating each individual patient. To that end, a major goal of current medical research is the rapid identification of the specific molecular alterations in each patient's disease. This will enable the design of optimal diagnosis, prognosis and treatment, significantly improving survival. This review describes one important approach to the genetic analysis of disease--molecular profiling--and the tenets and technologies necessary for its success.

DNA Fingerprinting↗

PubMed2006

Investigation of the molecular profile of basal cell carcinoma using whole genome microarrays.

BACKGROUND: Skin cancer accounts for 1/3 of all newly diagnosed cancer. Although seldom fatal, basal cell carcinoma (BCC) is associated with severe disfigurement and morbidity. BCC has a unique interest for researchers, as although it is often locally invasive, it rarely metastasises. This paper, reporting the first whole genome expression microarray analysis of skin cancer, aimed to investigate the molecular profile of BCC in comparison to non-cancerous skin biopsies. RNA from BCC and normal skin specimens was analysed using Affymetrix whole genome microarrays. A Welch t-test was applied to data normalised using dCHIP to identify significant differentially-expressed genes between BCC and normal specimens. Principal component analysis and support vector machine analysis were performed on resulting genelists, Genmapp was used to identify pathways affected, and GOstat aided identification of areas of gene ontology more highly represented on these lists than would be expected by chance. RESULTS: Following normalisation, specimens clustered into groups of BCC specimens and of normal skin specimens. Of the 54,675 gene transcripts/variants analysed, 3,921 were differentially expressed between BCC and normal skin specimens. Of these, 2,108 were significantly up-regulated and 1,813 were statistically significantly down-regulated in BCCs. CONCLUSION: Functional gene sets differentially expressed include those involved in transcription, proliferation, cell motility, apoptosis and metabolism. As expected, members of the Wnt and hedgehog pathways were found to be significantly different between BCC and normal specimens, as were many previously undescribed changes in gene expression between normal and BCC specimens, including basonuclin2 and mrp9. Quantitative-PCR analysis confirmed our microarray results, identifying novel potential biomarkers for BCC.

Aged↗

PubMed1992

On the molecular profiling of cell surfaces by SEM.

Cell surfaces interface with a variety of environments and, as a consequence, cell surface properties are of considerable functional importance to the biological organism. SEM immunocytochemistry (SEM-IC) is one of a range of techniques used to analyse cell surface properties. A major goal of SEM-IC centres on extended survey or high-magnification morphological analysis of cell and tissue surfaces combined with molecular profiles of these surfaces as established by gold-labelling. The properties of colloidal gold make it the marker of choice for SEM-IC and a representative gold-labelling protocol is outlined. The SEM-IC gold-labelling technique has been applied advantageously to the analysis both of cell surfaces and cytoskeletal and extracellular matrix elements: a tabulation of the main SEM-IC biomedical applications is given. Illustrated examples demonstrate how SEM-IC provides a highly effective approach for analysis both of cell and tissue differentiation-maturation sequences, and of pathological change involving not only the entire tissue or cell surface but also minute changes in microdomain characteristics of the individual cell surface. Steps in exploiting the technique of colloidal gold SEM-IC have been several-fold and include: use of backscattered electron imaging; accurate localization of gold particles by superimposition on topographical maps of the cell surface; and use of small (1-10 nm) gold probes followed by silver enhancement in order to minimize steric hindrance. Factors under assessment include: use of low voltage SEM; BE imaging of samples coated with ultrathin metal films; and use of gold-labelled SEM-IC for direct quantification of the numbers of target molecules exposed on cell surfaces by automated image analysis of the digitized BE image.

Animals↗

PubMed2006

Molecular profiling of cervical neoplasia.

Cervical cancer, a potentially preventable disease, remains the second most common malignancy in women worldwide. Human papillomavirus is the single most important etiological agent in cervical cancer, contributing to neoplastic progression through the action of viral oncoproteins, mainly E6 and E7, which interfere with critical cell cycle pathways, p53 and retinoblastoma. However, evidence suggests that human papillomavirus infection alone is insufficient to induce malignant changes and that other host genetic variations are important in the development of cervical cancer. This article will discuss the latest molecular profiling techniques available and review the published literature relating to their role in the diagnosis and management of cervical dysplasia and cancer. It is hoped that these techniques will allow the detection of novel biomarkers at DNA, RNA, microRNA and protein levels, which may ultimately play a role in facilitating early disease diagnosis and in predicting response to therapies, thus allowing the development of personalized treatment strategies.

Biomarkers, Tumor↗

PubMed2005

How molecular profiling could revolutionize drug discovery.

Information from genomic, proteomic and metabolomic measurements has already benefited target discovery and validation, assessment of efficacy and toxicity of compounds, identification of disease subgroups and the prediction of responses of individual patients. Greater benefits can be expected from the application of these technologies on a significantly larger scale; by simultaneously collecting diverse measurements from the same subjects or cell cultures; by exploiting the steadily improving quantitative accuracy of the technologies; and by interpreting the emerging data in the context of underlying biological models of increasing sophistication. The benefits of applying molecular profiling to drug discovery and development will include much lower failure rates at all stages of the drug development pipeline, faster progression from discovery through to clinical trials and more successful therapies for patient subgroups. Upheavals in existing organizational structures in the current 'conveyor belt' models of drug discovery might be required to take full advantage of these methods.

Animals↗

PubMed2004

Ectopic expression of Hoxd10 in thoracic spinal segments induces motoneurons with a lumbosacral molecular profile and axon projections to the limb.

Hox genes encode anterior-posterior identity during central nervous system development. Few studies have examined Hox gene function at lumbosacral (LS) levels of the spinal cord, where there is extensive information on normal development. Hoxd10 is expressed at high levels in the embryonic LS cord but not the thoracic cord. To test the hypothesis that restricted expression of Hoxd10 contributes to the attainment of an LS identity, and specifically an LS motoneuron identity, Hoxd10 was ectopically expressed in thoracic segments in chick embryos by means of in ovo electroporation. Regional motoneuron identity was assessed after the normal period of motoneuron differentiation. Subsets of motoneurons in transfected thoracic segments developed a molecular profile normally shown by LS motoneurons, including Lim 1 and RALDH2 expression. In addition, motoneurons in posterior thoracic segments showed novel axon projections to two muscles in the anterodorsal limb, the sartorius and anterior iliotibialis muscles. At thoracic levels, we also found a decrease in motoneuron numbers and a reduction in gonad size. These last findings suggest that early and high levels of Hox expression impeded motoneuron development and neural-mesodermal interactions. Despite these adverse effects, our data indicate that Hoxd10 expression is sufficient to induce LS motoneuron identity and axon trajectories characteristic of motoneurons in the LS region.

Aldehyde Oxidoreductases↗

PubMed2005

Exploiting naturally occurring DNA variation and molecular profiling data to dissect disease and drug response traits.

Identifying the key drivers of common human diseases and associated signaling pathways remains one of the primary objectives in the biomedical and life sciences. In this respect, common inbred strains of mice have played a crucial role, and recent advances in the development of genomics and bioinformatics tools have significantly enhanced their utility for this purpose. These advances have enabled a more holistic, network-oriented view of biological systems that facilitates elucidation of the underlying causes of disease and the best ways to target them. Success in reconstructing gene networks underlying disease traits (or other complex traits like drug response) and identifying the key drivers of these traits now largely rests on integrative approaches that combine data from multiple different sources. Such integrative genomics approaches that take into account genotypic, molecular profiling and clinical data in segregating mouse populations have recently been developed. Key to this integration has been the development and application of sophisticated algorithms to mine the diversity of data.

Algorithms↗

PubMed2005

Evidence by molecular profiling for a placental origin of infantile hemangioma.

The origin of the pathogenic endothelial cells in common infantile hemangioma is unknown. We show here that the transcriptomes of human placenta and infantile hemangioma are sufficiently similar to suggest a placental origin for this tumor, expanding on recent immunophenotypical studies that have suggested this possibility [North, P. E., et al. (2001) Arch. Dermatol. 137, 559-570]. The transcriptomes of placenta, hemangioma, and eight normal and diseased tissues were compared by hierarchical and nonhierarchical clustering analysis of >7,800 genes. We found that the level of transcriptome similarity between placenta and hemangioma exceeded that of any other tissue compared and paralleled that observed between a given tissue and its derived tumor, such as normal and cancerous lung. The degree of similarity was even greater when a subset of endothelial cell-specific genes was analyzed. Genes preferentially expressed in both placenta and hemangiomas were identified, including 17-beta hydroxysteroid dehydrogenase type 2 and tissue factor pathway inhibitor 2. These data demonstrate the value of global molecular profiling of tissues as a tool for hypothesis-driven research. Furthermore, it suggests that the unique self-limited growth of infantile hemangioma may, in fact, mirror the lifetime of placental endothelium.

17-Hydroxysteroid Dehydrogenases↗

PubMed2006

High-throughput molecular profiling of blood donors for minor red blood cell and platelet antigens.

BACKGROUND: ABO and D phenotyping of both blood donors and patients receiving transfusions is routinely performed by blood banks to ensure compatibility. These analyses are performed by antibody-based agglutination assays. Blood is not tested for minor blood group antigens on a regular basis, however, because of cost and time constraints. This can result in alloimmunization of the patient against one to several minor antigens and may complicate future transfusions. STUDY DESIGN AND METHODS: To address this problem, an assay has been generated on the GenomeLab SNPstream genotyping system to test simultaneously polymorphisms linked to 22 different blood antigens with donor's DNA isolated from minute amounts of white blood cells. RESULTS: The results showed that both the error rate of the assay, as measured by the strand concordance rate, and the no-call rate were very low (0.1%). The concordance rate with the actual red blood cell (RBC) and platelet (PLT) serology data varied from 97 to 100 percent. Experimental or database errors as well as rare polymorphisms contributing to antigen conformation could explain the observed differences. These rates, however, are well above requirements because phenotyping and cross-matching will always be performed before transfusion. CONCLUSION: Molecular profiling of blood donors for minor RBC and PLT antigens will give blood banks instant access to many different matched donors through the setup of a centralized data storage system.

ABO Blood-Group System↗