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Biomedical subjects

C M Chuong

Publications and source records attributed to C M Chuong.

At least 19 recordsLinked to original sources
PubMed2006

What is the biological basis of pattern formation of skin lesions?

Pattern recognition is at the heart of clinical dermatology and dermatopathology. Yet, while every practitioner of the art of dermatological diagnosis recognizes the supreme value of diagnostic cues provided by defined patterns of 'efflorescences', few contemplate on the biological basis of pattern formation in and of skin lesions. Vice versa, developmental and theoretical biologists, who would be best prepared to study skin lesion patterns, are lamentably slow to discover this field as a uniquely instructive testing ground for probing theoretical concepts on pattern generation in the human system. As a result, we have at best scraped the surface of understanding the biological basis of pattern formation of skin lesions, and widely open questions dominate over definitive answer. As a symmetry-breaking force, pattern formation represents one of the most fundamental principles that nature enlists for system organization. Thus, the peculiar and often characteristic arrangements that skin lesions display provide a unique opportunity to reflect upon--and to experimentally dissect--the powerful organizing principles at the crossroads of developmental, skin and theoretical biology, genetics, and clinical dermatology that underlie these--increasingly less enigmatic--phenomena. The current 'Controversies' feature offers a range of different perspectives on how pattern formation of skin lesions can be approached. With this, we hope to encourage more systematic interdisciplinary research efforts geared at unraveling the many unsolved, yet utterly fascinating mysteries of dermatological pattern formation. In short: never a dull pattern!

Algorithms↗
PubMed2002

What is the 'true' function of skin?

Conventional textbook wisdom portrays the skin as an organ that literally enwraps whatever each of us stands for as a more or less functional, individual member of the mammalian species, and has it that the skin primarily establishes, controls and transmits contacts with the external world. In addition, the skin has long been recognized to protect the organism from deleterious environmental impacts (physical, chemical,microbiological), and is well-known as crucial for the maintenance of temperature, electrolyte and fluid balance. Now, ever more studies are being published that show the skin to also operate as a huge and highly active biofactory for the synthesis,processing and/or metabolism of an astounding range of e.g. structural proteins, glycans, lipids and signaling molecules. Increasingly, it becomes appreciated that the skin, furthermore, is an integral component of the immune, nervous and endocrine systems, with numerous lines of cross-talk between these systems established intracutaneously (e.g. Ann NY Acad Sci Vol 885, 1999; Endocrine Rev 21:457-487, 2000; Physiol Rev 80:980-1020, 2001; Exp Dermatol 10: 349-367, 2001). All these emerging cutaneous functions beyond the classical image of the skin as a barrier and sensory organ are immediately relevant for many of the quandaries that clinical dermatology, dermatopathology, and dermatopharmacology are still struggling with to-date, and offer the practising dermatologist attractive new targets for therapeutic intervention. Yet, many of these skin functions are not even mentioned in dermatology textbooks and await systematic therapeutic targeting. Following a suggestion by Enno Christophers, the current 'Controversies' feature brings together an unusually diverse council of biologists and clinicians, who share their thought-provoking views with the readers and allow us to peek into the future of research in cutaneous biology, not the least by reminding us of the -- often ignored -- evolutionary and embryonal origins of our favorite organ. Hopefully, this unique discussion feature will foster an understanding of the 'true' skin functions that is both more comprehensive and more profound than conventional teaching on this topic, and will stimulate more than 'skin-deep' reflections on the full range of skin functions.

Aging↗
PubMed2001

A Novel mRNA-cDNA interference phenomenon for silencing bcl-2 expression in human LNCaP cells.

The templates required for inducing posttranscriptional gene silencing (PTGS) effects have been investigated in human prostate cancer LNCaP cells. Transfection of a mRNA-cDNA hybrid construct was found to result in a relatively long-term interference of specific gene expression. Androgen-stimulated expression of bcl-2 has been reported to increase the tumorigenic and metastatic potentials of human prostate cancer LNCaP cells, as well as their resistance to many apoptotic stimuli. The addition of bcl-2 antisense oligonucleotides, however, restored apoptosis. Our studies demonstrate gene silencing effects of the mRNA-cDNA transfection that is similar to those of PTGS/RNAi in this in vitro prostate cancer cell model. A potential RNA-directed RNA polymerase activity was also detected which is alpha-amanitin-sensitive. These findings indicate that a novel gene silencing system may exist in mammalian cells.

Base Sequence↗
PubMed2001

D-RNAi (messenger RNA-antisense DNA interference) as a novel defense system against cancer and viral infections.

D-RNAi (Messenger RNA-antisense DNA interference), a novel posttranscriptional phenomenon of silencing gene expression by transfection of mRNA-aDNA hybrids, was originally observed in the effects of bcl-2 on phorbol ester-induced apoptosis in human prostate cancer LNCaP cells. This phenomenon was also demonstrated in chicken embryos and a human CD4(+) T cell line, H9. The in vivo transduction of beta-catenin D-RNAi was shown to knock out more than 99% endogenous beta-catenin gene expression, while the in cell transfection of HIV-1 D-RNAi homolog rejected viral gene replication completely. D-RNAi was found to have long-term gene knockout effects resulting from a posttranscriptional gene silencing mechanism that may involve the homologous recombination between intracellular mRNA and the mRNA components of a D-RNAi construct. These findings provide a potential intracellular defense system against cancer and viral infections.

DNA, Antisense↗
PubMed2001

Immunohistochemical localization of deleted-in-colon-cancer (DCC) protein in human epithelial, neural, and neuro-endocrine tissues in paraffin sections with antigen retrieval.

A gene called deleted in colon cancer (DCC) has been identified on a region of chromosome 18, which is deleted in 70% of colorectal cancers. The DCC gene encodes a protein belonging to the immunoglobulin superfamily with similarity to the N-CAM transmembrane proteins, and it is a putative tumor-suppressor gene. Alternative splicing of transcripts of transmembrane proteins, including N-CAM, is know to occur, resulting in different isoforms of the protein. Using a polyclonal antibody against the DCC gene product, we have demonstrated, by antigen retrieval immunostaining, the presence of a DCC protein isoform on the cell surface of goblet cells in the G-I tract, cytoplasm of squamous epithelium in the skin & esophagus and transitional epithelium in the urinary bladder, ductal glandular epithelium of endometrium, endocervix, prostate, gall bladder and breast, cytoplasm of neuron in the cerebral cortex and Purkinje cells in the cerebellum. In addition, we also demonstrated DCC protein expression in neuroendocrine cells including argentaffin cells of the stomach, small intestine, appendix and colon, C cells of thyroid gland, chromaffin cells of the adrenal gland, islets of Langerhans in the pancreas and neurons of the sympathetic ganglion. This restrictive distribution suggests the DCC gene products may be abundant expression in neuroendocrine cells of human tissue.

Animals↗
PubMed2000

Conservation of early odontogenic signaling pathways in Aves.

Teeth have been missing from birds (Aves) for at least 60 million years. However, in the chick oral cavity a rudiment forms that resembles the lamina stage of the mammalian molar tooth germ. We have addressed the molecular basis for this secondary loss of tooth formation in Aves by analyzing in chick embryos the status of molecular pathways known to regulate mouse tooth development. Similar to the mouse dental lamina, expression of Fgf8, Pitx2, Barx1, and Pax9 defines a potential chick odontogenic region. However, the expression of three molecules involved in tooth initiation, Bmp4, Msx1, and Msx2, are absent from the presumptive chick dental lamina. In chick mandibles, exogenous bone morphogenetic protein (BMP) induces Msx expression and together with fibroblast growth factor promotes the development of Sonic hedgehog expressing epithelial structures. Distinct epithelial appendages also were induced when chick mandibular epithelium was recombined with a tissue source of BMPs and fibroblast growth factors, chick skin mesenchyme. These results show that, although latent, the early signaling pathways involved in odontogenesis remain inducible in Aves and suggest that loss of odontogenic Bmp4 expression may be responsible for the early arrest of tooth development in living birds.

Animals↗
PubMed2000

beta-catenin in epithelial morphogenesis: conversion of part of avian foot scales into feather buds with a mutated beta-catenin.

We explored the role of beta-catenin in chicken skin morphogenesis. Initially beta-catenin mRNA was expressed at homogeneous levels in the epithelia over a skin appendage tract field which became transformed into a periodic pattern corresponding to individual primordia. The importance of periodic patterning was shown in scaleless mutants, in which beta-catenin was initially expressed normally, but failed to make a punctuated pattern. To test beta-catenin function, a truncated armadillo fragment was expressed in developing chicken skin from the RCAS retrovirus. This produced a variety of phenotypic changes during epithelial appendage morphogenesis. In apteric and scale-producing regions, new feather buds with normal-appearing follicle sheaths, dermal papillae, and barb ridges were induced. In feather tracts, short, wide, and curled feather buds with abnormal morphology and random orientation formed. Epidermal invaginations and placode-like structures formed in the scale epidermis. PCNA staining and the distribution of molecular markers (SHH, NCAM, Tenascin-C) were characteristic of feather buds. These results suggest that the beta-catenin pathway is involved in modulating epithelial morphogenesis and that increased beta-catenin pathway activity can increase the activity of skin appendage phenotypes. Analogies between regulated and deregulated new growths are discussed.

Adenomatous Polyposis Coli Protein↗
PubMed2000

Dynamic expression of lunatic fringe during feather morphogenesis: a switch from medial-lateral to anterior-posterior asymmetry.

Expression of Lunatic fringe mRNA was studied during feather morphogenesis and showed three stages of dynamic expression pattern. (1) Lunatic fringe was first expressed in the epithelium as a ring bordering the feather primordium when it was initially induced. (2) Shortly after, it showed a polarized pattern, first toward the lateral side of the feather primordium and then made a 90 degrees C switch toward the posterior side of the short bud. It then becomes weakly expressed in the long bud stage. (3) Finally, it is expressed in the marginal plate epithelia of feather filaments. In contrast, Radical fringe is weakly expressed in the feather bud, but is also present in the marginal plate epithelia of feather filaments.

Animals↗
PubMed2000

Sonic hedgehog signaling pathway in vertebrate epithelial appendage morphogenesis: perspectives in development and evolution.

Vertebrate epithelial appendages are elaborate topological transformations of flat epithelia into complex organs that either protrude out of external (integument) and internal (oral cavity, gut) epithelia, or invaginate into the surrounding mesenchyme. Although they have specific structures and diverse functions, most epithelial appendages share similar developmental stages, including induction, morphogenesis, differentiation and cycling. The roles of the SHH pathway are analyzed in exemplary organs including feather, hair, tooth, tongue papilla, lung and foregut. SHH is not essential for induction and differentiation, but is involved heavily in morphogenetic processes including cell proliferation (size regulation), branching morphogenesis, mesenchymal condensation, fate determination (segmentation), polarizing activities and so on. Through differential activation of these processes by SHH in a spatiotemporal-specific fashion, organs of different shape and size are laid down. During evolution, new links of developmental pathways may occur and novel forms of epithelial appendages may emerge, upon which evolutionary selections can act. Sites of major variations have progressed from the body plan to the limb plan to the epithelial appendage plan. With its powerful morphogenetic activities, the SHH pathway would likely continue to play a major role in the evolution of novel epithelial appendages.

Animals↗
PubMed1999

In vivo analysis of cancerous gene expression by RNA-polymerase chain reaction.

An easy and routine procedure to amplify messenger RNA (mRNA) libraries from a few tissue cells can provide molecular gene expression profiles at high resolution. A novel PCR-like method, the RNA-PCR, was developed to generate high quality and quantity mRNAs from as few as 20 cells (2 pg mRNAs). The principle relies upon the cycling steps of promoter-linked double-stranded cDNA synthesis and promoter-driven transcription to amplify mRNAs up to 250-fold/cycle with good representation of high and low copy mRNAs. The amplified mRNA libraries were shown to possess high fidelity, purity, specificity and reproducibility for in vivo analyses of cancerous gene expression in human prostate cancers.

Base Sequence↗
PubMed1999

Suppression of activin-induced apoptosis by novel antisense strategy in human prostate cancer cells.

Apoptosin, a novel gene encoding a mitotic kinase-motif protein, is stimulated by activin, a member of TGF-beta family, in human LNCaP prostate cancer cells and in patient tissues. We employed a gene knockout methodology based on the covalent bonding of chemically modified antisense probes to apoptosin mRNAs in LNCaP cells. The mRNA-antisense hybrid duplexes were neither translated nor post-transcriptionally modified, resulting in no protein synthesis. Introducing antisense apoptosin into activin-induced apoptotic LNCaP cells prevented apoptosis, interfered with genomic DNA fragmentation and released cell cycle checkpoint. These findings suggest that the apoptosin, in addition to p53, is important in apoptotic regulation of human prostate cancers.

Activins↗
PubMed1999

Successive formative stages of precartilaginous mesenchymal condensations in vitro: modulation of cell adhesion by Wnt-7A and BMP-2.

High-density chick limb bud cell culture is a useful model to study mesenchymal condensatifons and chondrogenesis. Most previous studies have focused on the effects of soluble reagents on terminal chondrogenic differentiation and have not defined the early cellular processes and signaling events. In this study, we defined five successive stages in the differentiation process: 1) dissociated cells, 2) small aggregates, 3) formation of cell clusters, 4) precartilaginous condensations, and 5) cartilage nodule. We used RCAS retrovirus-mediated Wnt-7a gene transduction to test the effect of Wnt-7a on the differentiation process. We found that Wnt-7a suppressed chondrogenic differentiation. Wnt-7a did not inhibit the initiation of condensation formation but blocked the progression of precartilaginous condensations to cartilage nodules. The Wnt-7a-transduced cultures showed characteristics of a less mature culture with persistent expression of NCAM, N-cadherin, wider distribution of integrin beta1 and fibronectin, and suppression of tenascin-C. BMP-2 is known to enhance chondrogenic differentiation in these cultures by promoting cell clusters to form continuous sheet-like precartilaginous condensations. However, cultures exposed to both BMP-2 and Wnt-7a showed inhibition of chondrogenic differentiation. Different signaling molecules such as Wnt-7a and BMP-2 may have antagonistic effects on cartilage differentiation and the gradient of the two molecules may be involved in defining the boundaries of the initial precartilaginous condensation. We propose that the shape of the precartilaginous condensations may be modulated by local concentrations of signaling molecules, such as Wnt-7a and BMP-2, which act to alter cell-substrate and cell-cell adhesions.

Animals↗
PubMed1999

Msx-2 and the regulation of organ size: epidermal thickness and hair length.

During organogenesis, the issue of size regulation is as important as shape and differentiation. We propose that the regulation of the dimensions of the epithelium and its appendages (length, width, thickness) are based on regulation of cell numbers in specific sites, reflecting the input and output of cells in that region. This process is in turn regulated by the flow from the domain of proliferating cells to the domain of postmitotic differentiated cells. When the homeobox gene Msx-2 is over-expressed in transgenic mice under the control of the CMV promoter, the epidermis is thickened with hyperproliferation and hyperkeratosis. Hairs are shorter and the matrix region is shrunken. We suggest that Msx-2 may be one of the regulators involved in the control of organ size, and the above phenotypes are the manifestations of an increased cellular flow from proliferation domain to differentiation domain in the tissue.

Animals↗
PubMed1999

Early events in skin appendage formation: induction of epithelial placodes and condensation of dermal mesenchyme.

The formation of skin appendages represents a morphogenetic process through which a homogeneous system is converted into a patterned system. We have pursued molecules involved in the early placode induction and mesenchymal condensation stages of this process. We found that intracellular and extracellular signaling molecules collaborate to position the location of feather primordia and initiate mesenchymal condensations mediated by adhesion molecules. During the inductive stage, cells interact in a fashion best described by a reaction-diffusion mechanism. Thus in early feather morphogenesis, low level adhesion molecules drive cell interactions. The interactions were modulated by extracellular signaling molecules, which eventually increase the level of signaling molecules at sites of feather initiation and subsequently the level of adhesion molecules (Jiang et al, 1999a). These physico-chemical events lead to the formation of dermal condensations and epithelial placodes at sites of feather primordia, thus achieving the earliest and most fundamental events of skin appendage formation: induction.

Animals↗
PubMed1999

Phenotypic determination of epithelial appendages: genes, developmental pathways, and evolution.

Epithelial appendages are derivatives of epithelia that elaborate to form specialized structures and functions. The appendage can protrude out, such as in teeth and feathers, or invaginate in, such as in glands. The epithelia can be ectodermal, such as in hairs, or endodermal, such as in livers. Using feather as a prototype of epithelial appendage, we study the molecular signals involved in the successive stages of epithelial-mesenchymal interactions during morphogenesis. We propose that these form the basics of gene networks, which can be integrated to gene supernetwork and totinetwork. Because the unit of development is molecular pathway rather than single molecule, and the unit of morphogenesis is cell group rather than single cell, we make the analogy between genes/developmental pathways and words/sentences. The study of developmental pathways in epithelial appendage organogenesis will help us to understand the grammar of genes and the basic rules in constructing regulated new growth. This knowledge may contribute to the study of cancer biology (deregulated new growth) and organ regeneration.

Animals↗