Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q16637 (SMA)
 8,107 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three canine osteosarcoma cell lines were established from spontaneous pelvic and radial osteosarcomas. The cell populations cultured exhibited characteristics of malignancy and consisted of adherent, pleomorphic, mostly large spindle-shaped or polyhedral cells, characterised by the presence of numerous cytoplasmic granules and vacuoles. The main ultrastructural features included the presence of abundant rough endoplasmic reticulum and numerous cytoplasmic vesicles, deposit vacuoles and small cytoplasmic protrusions. Zymography showed that the cell lines produce high levels of MMP-2 and MMP-9, enzymes directly involved in crucial aspects of the metastatic process. Consistent with their osteoblastic lineage and malignant phenotype, all cell lines were immunoreactive to vimentin, osteopontin, PCNA, p53, MMP-2 and MMP-9, while they were negative for cytokeratin, desmin, SMA, Factor VIII, NSE, GFAP, Rb and p21 protein. No retroviral particles or RNA were detected ultrastructurally or with RT-PCR, although the possibility of viral involvement in osteosarcoma cannot be excluded. The new cell lines provide excellent in vitro models that may allow further studies on the pathobiology of canine osteosarcoma to be undertaken.
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PMID:Characterisation of three novel canine osteosarcoma cell lines producing high levels of matrix metalloproteinases. 1519 3

Seventeen cases of canine peripheral nerve sheath tumors (PNSTs), 11 malignant PNSTs (MPNSTs), and six benign PNSTs (BPNSTs) were examined. The prognosis in five of six dogs with BPNSTs was excellent, whereas all dogs with MPNSTs died within 2 years after the last surgical resection. One BPNST formed a recurrent mass with features of a MPNST. Histopathologically, the predominant tumor cell of MPNSTs was either spindle or round in shape with epithelioid characteristics. Other atypical cells had abundant granular cytoplasm or were multinucleated giant cells with periodic acid-Schiff-positive cytoplasmic globules. Furthermore, two MPNSTs contained cartilaginous and osseous metaplasia. On the contrary, most BPNSTs exhibited typical features of schwannoma or neurofibroma, whereas two BPNSTs had atypical morphology. One BPNST consisted of epithelioid cell proliferation with some tumor cells revealing nuclear atypia. Immunohistochemically, the expression of vimentin (100%), S-100 (73%), nerve growth factor receptor (NGFR, 64%), and myoglobin (64%) was commonly found in MPNSTs. The two BPNSTs with atypical histologic appearances were positive for vimentin, S-100, NGFR, and neuron-specific enolase, and one of these had moderate immunoreactivity for cytokeratin. Most BPNSTs were positive for glial fibrillary acidic protein, as well as S-100 and NGFR. Although most rhabdomyosarcomas (RMSs) and canine hemangiopericytomas (CHPs) also showed focal immunoreactivity for S-100, most RMSs were intensely positive for myoglobin and negative for NGFR. Most CHPs (80%) exhibited focal alpha-smooth muscle actin (alpha-SMA) expression, whereas all PNSTs were negative. These results indicate that immunohistochemistry for NGFR and alpha-SMA might be useful for differentiating canine PNSTs from RMSs or CHPs, respectively.
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PMID:Immunohistochemical evaluation of canine peripheral nerve sheath tumors and other soft tissue sarcomas. 1523 30

Tissue engineering of heart valves utilizes biodegradable or metabolizable scaffolds for remodeling by seeded autologous cells. The aim of this study was to determine and compare extracellular matrix (ECM) formations, cellular phenotypes and cell location of native and tissue engineered (TE) valve leaflets. Ovine carotid arteries, ovine and porcine hearts were obtained from slaughterhouses. Cells were isolated from carotid arteries and dissected ovine, porcine and TE leaflets. TE constructs were fabricated from decellularized porcine pulmonary valves, seeded ovine arterial cells and subsequent 16 days dynamic in vitro culture using a pulsatile bioreactor. Native and TE valves were studied by histology (hematoxylin-eosin, resorcin-fuchsin, Movat pentachrome), NIR femtosecond multiphoton laser scanning microscopy and scanning electron microscopy (SEM). Cells of native and TE tissues were identified and localized by immunohistochemistry. Arterial, valvular and re-isolated TE-construct cells were processed for immunocytochemistry and Western blotting. ECM analysis and SEM revealed characteristical and comparable structures in native and TE leaflets. Most cells in native leaflets stained strongly positive for vimentin. Cells positive to alpha-smooth muscle actin (alpha-SMA), myosin and calponin were only found at the ventricular (inflow) side of ovine aortic and porcine pulmonary valve leaflets. Cells from TE constructs had a strong expression of vimentin, alpha-SMA, myosin, calponin and h-caldesmon throughout the entire leaflet. Comparable ECM formation and endothelial cell lining of native and TE leaflets could be demonstrated. However, immunostaining revealed significant differences between valvular cell phenotypes of native and TE leaflets. These results may be essential for further cardiovascular tissue engineering efforts.
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PMID:Comparative study of cellular and extracellular matrix composition of native and tissue engineered heart valves. 1524 10

Stromal cells and extracellular matrix (ECM) components are important for tumour cell behaviour. Little is known about the role of stromal cells and ECM components in the progression and regression of spontaneous canine transmissible venereal tumour (CTVT). In this study, the stromal cell type was determined by immunohistochemical labelling with antibodies to desmin, vimentin and alpha-smooth muscle actin (alpha-SMA) during the progressive and regressive stages of spontaneous CTVT. The distribution of ECM components tenascin-C, chondroitin sulphate and versican were determined immunohistochemically, and hyaluronan distribution was determined using a biotinylated protein complex with specific affinity for hyaluronan. Stromal cells of tumours in both the progressive and regressive stage were positive for vimentin and negative for desmin. The number of stromal cells expressing alpha-SMA was significantly higher (P=0.001) in regressing tumours, than progressing tumours. These results suggest that the modulation of stromal cells that occurs during the regression of CTVT is similar to that occurring during wound healing. Tenascin-C was weakly expressed in the stroma of tumours in the progressive stage and in regions of the regressing tumours with tumour infiltrating lymphocytes (TILs), but intensely expressed in the stroma of tumours in late regressive stage. In addition, tenascin-C was also expressed in the cytoplasm of some tumour cells in the late regressive stage. A strong stromal tenascin-C intensity was significantly associated with regressing tumours (P=0.001). Strong stromal hyaluronan intensity and a high proportion of hyaluronan-positive tumour cells were significantly associated with progressing tumours (P=0.001). This suggests that hyaluronan is involved in the growth of the tumour. There was no significant difference in the expression of chondroitin sulphate and versican in progressing and regressing tumours.
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PMID:Stromal cells and extracellular matrix components in spontaneous canine transmissible venereal tumour at different stages of growth. 1537 54

Connective tissue growth factor (CTGF) has been reported to play an important role in mediating the profibrotic effects of transforming growth factor-beta (TGF-beta) in various renal diseases. To elucidate the role of CTGF in renal tubular epithelial-myofibroblast transdifferentiation, we examined the expression of alpha-smooth muscle actin (alpha-SMA), vimentin, tenascin-C, and collagen IV expression upon the stimulation of CTGF in cultured human proximal tubular epithelial cell line (HKC), and further investigated the effects of endogenous CTGF blockade on the transdifferentiation process induced by TGF-beta. It is revealed that upon the stimulation of recombinant human CTGF (rhCTGF, 2.5 or 5.0 microg/L), the expression of alpha-SMA and tenascin-C mRNA increased significantly (p<0.01), while collagen IV gene expression decreased significantly (p<0.01), all in a dose-dependent manner. The percentage of alpha-SMA-positive cells was significantly larger in the rhCTGF-stimulated groups than that in negative control (38.9%, 65.5% vs. 2.4%, respectively, p<0.01) as confirmed by flow cytometry. Both cytoplasmic and secretory tenascin-C expression was upregulated by the stimulation of rhCTGF (p<0.01). Under this condition, collagen IV secreted into the culture media was lowered markedly (p<0.01). On RT-PCR analysis, TGF-beta1 upregulated CTGF gene expression, preceding that of alpha-SMA. The alpha-SMA mRNA expression induced by TGF-beta1 was significantly inhibited by CTGF antisense oligodeoxynucleotide (ODN) transfection (p<0.01). With prolonged incubation time, CTGF antisense ODN also inhibited intracellular alpha-SMA protein synthesis, as demonstrated by indirect immuno-fluorescence. So it is concluded that CTGF could promote the transdifferentiation of human renal tubular epithelial cells towards myofibroblasts in vitro, both directly and as a downstream mediator of TGF-beta, and CTGF blockade would be a possible therapeutic target against tubulointerstitial fibrosis.
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PMID:Connective tissue growth factor regulates the key events in tubular epithelial to myofibroblast transition in vitro. 1556 56

Several experimental models have been developed for the study of the polycystic ovarian syndrome in the rat. In the present study, the syndrome was induced by exposure to constant light, and the expression of cytoskeletal proteins in the follicular wall was evaluated by immunohistochemistry. We analyzed the immunohistochemically stained area (IHCSA) by image analysis to evaluate the expression of intermediate filaments (vimentin, desmin, cytokeratins, gliofibrillary acidic protein and neurofilaments) and alpha-smooth muscle actin (alpha-SMA) in cystic ovaries in relation to normal ovaries. The granulosa cell layer of cystic follicles had a significantly greater IHCSA for vimentin than the normal antral follicles. This difference was also significant between atretic and antral follicles. Cytokeratins showed a very low expression in the granulosa cells of antral follicles of control ovaries while in granulosa cells of atretic and cystic follicles they showed a significantly higher IHCSA. Immunohistochemical localization of desmin and alpha-SMA was restricted to the theca externa. Immunoreactivity for gliofibrillary acidic protein and neurofilament was negative. The highest intensity in the staining with vimentin and cytokeratins observed in the granulosa cells of the cystic follicles is probably due to structural and functional changes that occur during the process of cystogenesis and they could be associated with intense changes in the expression of cytoskeletal proteins that may be essential to the proper cellular functioning.
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PMID:Expression of cytoskeletal proteins in the follicular wall of induced ovarian cysts. 1560 34

We investigated 20 spindle cell (sarcomatoid) metaplastic carcinomas (MCs) without squamous differentiation. In addition, five high-grade phyllodes tumors were assessed for comparison. Our immunohistochemical antibody panel included pan-cytokeratin (CK), low molecular weight CK (CK8/18), four basal cell type CKs (34betaE12, CK5/6, CK14, and CK17), vimentin antibodies, as well as antibodies to established (SMA, CD10, p63, S-100, maspin, calponin, GFAP, SM-myosin), and novel (CD29, 14-3-3sigma) myoepithelial markers. Sixteen of the 20 tumors (80%) expressed at least two markers of the combination CD10/p63/SMA. S-100 detected 1 case negative for CD10/p63/SMA and 3 cases that only expressed one marker of this combination. While 18 MCs (90%) were positive for CD29, 14-3-3sigma (11 cases) and maspin (9 cases) were observed in 55% and 45%, respectively. Antibodies to pan-CK and the basal cell type CKs were strongly reactive in 12 tumors (60%), but in 6 cases (30%) positivity for these markers was weak and only focal; 2 MCs showed no positivity for CK. The stromal component of all phyllodes tumors was positive for vimentin, whereas all other investigated markers were absent except for focal p63 and CD10 expression in 1 case each. Our findings convincingly show a myoepithelial immunophenotype in sarcomatoid MCs, which is demonstrated by the presence of basal cell type CKs and the combination of the established myoepithelial markers CD10, p63, SMA, and S-100. We conclude that tumors with weak or even absent CK expression should only be diagnosed as primary sarcomas of the breast after exclusion of a myoepithelial immunophenotype. CD29 and 14-3-3sigma represent valuable novel myoepithelial markers in these diagnostically difficult cases.
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PMID:Metaplastic breast carcinomas: are they of myoepithelial differentiation?: immunohistochemical profile of the sarcomatoid subtype using novel myoepithelial markers. 1572 3

Vimentin expression is a rather rare finding in invasive breast cancer, and is associated with high tumour invasiveness and chemoresistance. It is currently explained by two different biological theories: direct histogenetic derivation from myoepithelial cells, and epithelial-mesenchymal transition (EMT) reflecting the end-stage of breast cancer dedifferentiation. In this study we aimed to obtain further insights into the biological hallmarks of these vimentin-expressing breast cancers. We applied immunohistochemistry for vimentin and 15 other differentiation markers to a series of 364 invasive breast cancer cases, using tissue microarray technology. 7.7% of all tumours expressed vimentin. Almost all of these cases (19/21) were Grade 3 invasive ductal carcinomas, and the majority (13/21) of these were associated with a ductal in situ component. Vimentin expression was also seen in the respective in situ components and correlated positively with the expression of SMA, CD10, CK 5, p53, Mib-1 and EGFR. A negative correlation was seen for the expression of CK 8/18 and the oestrogen receptor. Vimentin-expressing carcinomas revealed a significantly higher average absolute number of cytogenetic alterations per case, but a significantly lower frequency of chromosome 16q losses compared to vimentin-negative cases. Our present results demonstrate that, despite analogies between vimentin-positive breast cancers and myoepithelial cells in their expression of differentiation-related proteins, neither myoepithelial histogenesis nor EMT can exclusively explain the biology of these distinct tumours. This is mainly supported by the significantly higher incidence of vimentin-expressing breast cancers compared to any other myoepithelial breast tumours and the fact that vimentin is already observed in ductal in situ components. We therefore propose the alternative hypothesis that vimentin-expressing breast carcinomas may derive from breast progenitor cells with bilinear (glandular and myoepithelial) differentiation potential.
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PMID:The origin of vimentin expression in invasive breast cancer: epithelial-mesenchymal transition, myoepithelial histogenesis or histogenesis from progenitor cells with bilinear differentiation potential? 1590 73

This case report describes a rare case of canalicular adenoma arising in the upper lip of a 61-year-old male patient. Macroscopic examination of the tumor revealed a well-defined, smooth, firm, elastic hard, round nodule with a diameter of 1.0 cm. The cut surface was white. Histopathology showed that the tumor was an encapsulated mass with a complex cellular pattern of anastomosing duct-like or trabecular structures lined by a single layer of tall columnar epithelial cells, which were embedded in a loose, fibrous, and highly vascular connective tissue stroma. The tumor cells were immunoreactive to AE1/AE3, CK19 and S-100, were partially positive for CK7, CK8, GFAP and PCNA, but were negative for SMA, CK13, CK14 and vimentin.
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PMID:Canalicular adenoma arising in the upper lip: review of the pathological findings. 1596 Jan 60

We describe here--presumably for the first time--a Cajal-like type of tubal interstitial cells (t-ICC), resembling the archetypal enteric ICC. t-ICC were demonstrated in situ and in vitro on fresh preparations (tissue cryosections and primary cell cultures) using methylene-blue, crystal-violet, Janus-Green B or MitoTracker-Green FM Probe vital stainings. Also, t-ICC were identified in fixed specimens by light microscopy (methylene-blue, Giemsa, trichrome stainings, Gomori silver-impregnation) or transmission electron microscopy (TEM). The positive diagnosis of t-ICC was strengthened by immunohistochemistry (IHC; CD117/c-kit+ and other 14 antigens) and immunofluorescence (IF; CD117/c-kit+ and other 7 antigens). The spatial density of t-ICC (ampullar-segment cryosections) was 100-150 cells/mm2. Non-conventional light microscopy (NCLM) of Epon semithin-sections revealed a network-like distribution of t-ICC in lamina propria and smooth muscle meshwork. t-ICC appeared located beneath of epithelium, in a 10-15 microm thick 'belt', where 18+/-2% of cells were t-ICC. In the whole lamina propria, t-ICC were about 9%, and in muscularis approximately 7%. In toto, t-ICC represent ~8% of subepithelial cells, as counted by NCLM. In vitro, t-ICC were 9.9+/-0.9% of total cell population. TEM showed that the diagnostic 'gold standard' (Huizinga et al., 1997) is fulfilled by 'our' t-ICC. However, we suggest a 'platinum standard', adding a new defining criterion- characteristic cytoplasmic processes (number: 1-5; length: tens of microm; thickness: < or =0.5 microm; aspect: moniliform; branching: dichotomous; organization: network, labyrinthic-system). Quantitatively, the ultrastructural architecture of t-ICC is: nucleus, 23.6+/-3.2% of cell volume, with heterochromatin 49.1+/-3.8%; mitochondria, 4.8+/-1.7%; rough and smooth endoplasmic-reticulum (1.1+/-0.6%, 1.0+/-0.2%, respectively); caveolae, 3.4+/-0.5%. We found more caveolae on the surface of cell processes versus cell body, as confirmed by IF for caveolins. Occasionally, the so-called 'Ca2+-release units' (subplasmalemmal close associations of caveolae+endoplasmic reticulum+mitochondria) were detected in the dilations of cell processes. Electrophysiological single unit recordings of t-ICC in primary cultures indicated sustained spontaneous electrical activity (amplitude of membrane potentials: 57.26+/-6.56 mV). Besides the CD117/c-kit marker, t-ICC expressed variously CD34, caveolins 1&2, alpha-SMA, S-100, vimentin, nestin, desmin, NK-1. t-ICC were negative for: CD68, CD1a, CD62P, NSE, GFAP, chromogranin-A, PGP9.5, but IHC showed the possible existence of (neuro)endocrine cells in tubal interstitium. We call them 'JF cells'. In conclusion, the identification of t-ICC might open the door for understanding some tubal functions, e.g. pace-making/peristaltism, secretion (auto-, juxta- and/or paracrine), regulation of neurotransmission (nitrergic/purinergic) and intercellular signaling, via the very long processes. Furthermore, t-ICC might even be uncommitted bipotential progenitor cells.
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PMID:Novel type of interstitial cell (Cajal-like) in human fallopian tube. 1596 70


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