scholarly journals Prevalence of the Hippo Effectors YAP1/TAZ in Tumors of Soft Tissue and Bone

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ilka Isfort ◽  
Sandra Elges ◽  
Magdalene Cyra ◽  
Ruth Berthold ◽  
Marcus Renner ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Nuclear Staining ◽  
Sarcoma Cell ◽  
Mesenchymal Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Active Pool ◽  
Myxoid Liposarcomas ◽  
Well Differentiated

AbstractTumors of soft tissue and bone represent a heterogeneous group of neoplasias characterized by a wide variety of genetic aberrations. Albeit knowledge on tumorigenesis in mesenchymal tumors is continuously increasing, specific insights on altered signaling pathways as a basis for molecularly targeted therapeutic strategies are still sparse. The aim of this study was to determine the involvement of YAP1/TAZ-mediated signals in tumors of soft tissue and bone. Expression levels of YAP1 and TAZ were analyzed by immunohistochemistry in a large cohort of 486 tumor specimens, comprising angiosarcomas (AS), Ewing sarcomas, leiomyosarcomas, malignant peripheral nerve sheath tumors (MPNST), solitary fibrous tumors, synovial sarcomas (SySa), well-differentiated/dedifferentiated/pleomorphic and myxoid liposarcomas (MLS). Moderate to strong nuclear staining of YAP1 and TAZ was detected in 53% and 33%, respectively. YAP1 nuclear expression was most prevalent in MPNST, SySa and MLS, whereas nuclear TAZ was predominately detected in AS, MLS and MPNST. In a set of sarcoma cell lines, immunoblotting confirmed nuclear localization of YAP1 and TAZ, corresponding to their transcriptionally active pool. Suppression of YAP1/TAZ-TEAD mediated transcriptional activity significantly impaired sarcoma cell viability in vitro and in vivo. Our findings identify nuclear YAP1 and TAZ positivity as a common feature in subsets of sarcomas of soft tissue and bone and provide evidence of YAP1/TAZ-TEAD signaling as a specific liability to be considered as a new target for therapeutic intervention. Nuclear YAP1/TAZ expression may represent a biomarker suited to identify patients that could benefit from YAP1/TAZ-TEAD directed therapeutic approaches within future clinical trials.

Evaluation of 99mTc-Label led Vitamin K4 as an Agent for Testicular Imaging

1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan
Keyword(s):  
Soft Tissue ◽  
Room Temperature ◽  
Normal Subjects ◽  
Left Testis ◽  
Wide Range ◽  
Activity Ratios ◽  
The Right ◽  
Radioactivity Levels

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.

scholarly journals Distribution of the Transcription Factors Sox9, AP-2, and [Delta]EF1 in Adult Murine Articular and Meniscal Cartilage and Growth Plate

2002 ◽  
Vol 50 (8) ◽  
pp. 1059-1065 ◽  
Author(s):  
Sherri R. Davies ◽  
Shinji Sakano ◽  
Yong Zhu ◽  
Linda J. Sandell
Keyword(s):  
Transcription Factors ◽  
Growth Plate ◽  
Type Ii Collagen ◽  
Nuclear Staining ◽  
Lower Growth ◽  
Biological Studies ◽  
Transcription In Vitro ◽  
Sox9 Protein

The control of extracellular matrix (ECM) production is important for the development, maintenance, and repair of cartilage tissues. Matrix molecule synthesis is generally regulated by the rate of gene transcription determined by DNA transcription factors. We have shown that transcription factors Sox9, AP-2, and [delta]EF1 are able to alter the rate of CD-RAP transcription in vitro: Sox9 upregulates, AP-2 exhibits biphasic effects, and [delta]EF1 represses expression of the CD-RAP gene. To correlate these in vitro activities in vivo, transcription factors were co-immunolocalized with ECM proteins in three different cartilage tissues in which the rates of biosynthesis are quite different: articular, meniscal, and growth plate. Immunoreactivities of type II collagen and CD-RAP were higher in growth plate than in either the articular or meniscal cartilages and correlated positively with Sox9 protein. Sox9 staining decreased with hypertrophy and was low in articular and meniscal cartilages. In contrast, AP-2 and [delta]EF1 were low in proliferating chondrocytes but high in lower growth plate, articular, and meniscal cartilages. This increase was also accompanied by intense nuclear staining. These immunohistochemical results are the first to localize both [delta]EF1 and AP-2 to adult articular, meniscal, and growth plate cartilages and provide in vivo correlation of previous molecular biological studies.

scholarly journals Quinolones for the Treatment ofNeisseria GonorrhoeaeandChlamydia Trachomatis

1993 ◽  
Vol 1 (2) ◽  
pp. 108-113 ◽  
Author(s):  
Sebastian Faro
Keyword(s):  
Urinary Tract ◽  
Soft Tissue ◽  
Chlamydia Trachomatis ◽  
Urinary Tract Infections ◽  
Single Agent ◽  
Moderate Activity ◽  
Sexually Transmitted ◽  
Tract Infections

The most commonly sexually transmitted bacteria areNeisseria gonorrhoeaeandChlamydia trachomatis.The quinolones ofloxacin and ciprofloxacin have been shown to have activity against both of these bacteria in vitro and in vivo. Ofloxacin is particularly well suited for the treatment ofN. gonorrhoeaeandC. trachomatiscervical infection, which can be considered the earliest manifestation of pelvic inflammatory disease (PID). Not only can ofloxacin be effectively used as a single agent, it is also useful in treating urinary tract infections caused by Enterobacteriaceae. Although it has moderate activity against anaerobes in general, ofloxacin does have activity against the anaerobes commonly isolated from female patients with soft tissue pelvic infections. Thus, ofloxacin has the potential for being utilized to treat early salpingitis.

scholarly journals A multi-center comparison of dual energy X-ray absorptiometers: In vivo and in vitro soft tissue measurement

1997 ◽  
Vol 51 (5) ◽  
pp. 312-317 ◽  
Author(s):  
CD Economos ◽  
ME Nelson ◽  
MA Fiatarone ◽  
GE Dallal ◽  
SB Heymsfield ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Dual Energy ◽  
X Ray

From local to global matrix organization by fibroblasts: a 4D laser-assisted bioprinting approach

2021 ◽  
Author(s):  
Camille Douillet ◽  
Marc Nicodeme ◽  
Loïc Hermant ◽  
Vanessa Bergeron ◽  
Fabien Guillemot ◽  
...  
Keyword(s):  
High Resolution ◽  
Soft Tissue ◽  
Dynamic Properties ◽  
Unmet Need ◽  
Specific Pattern ◽  
Matrix Remodeling ◽  
Collagen Gels ◽  
Lattice Contraction

Abstract Fibroblasts and myofibroblasts play a central role in skin homeostasis through dermal organization and maintenance. Nonetheless, the dynamic interactions between (myo)fibroblasts and the extracellular matrix (ECM) remain poorly exploited in skin repair strategies. Indeed, there is still an unmet need for soft tissue models allowing to study the spatial-temporal remodeling properties of (myo)fibroblasts. In vivo, wound healing studies in animals are limited by species specificity. In vitro, most models rely on collagen gels reorganized by randomly distributed fibroblasts. But biofabrication technologies have significantly evolved over the past ten years. High-resolution bioprinting now allows to investigate various cellular micropatterns and the emergent tissue organizations over time. In order to harness the full dynamic properties of cells and active biomaterials, it is essential to consider “time” as the 4th dimension in soft tissue design. Following this 4D bioprinting approach, we aimed to develop a novel model that could replicate fibroblast dynamic remodeling in vitro. For this purpose, (myo)fibroblasts were patterned on collagen gels with laser-assisted bioprinting (LAB) to study the generated matrix deformations and reorganizations. First, distinct populations, mainly composed of fibroblasts or myofibroblasts, were established in vitro to account for the variety of fibroblastic remodeling properties. Then, LAB was used to organize both populations on collagen gels in even isotropic patterns with high resolution, high density and high viability. With maturation, bioprinted patterns of fibroblasts and myofibroblasts reorganized into dispersed or aggregated cells, respectively. Stress-release contraction assays revealed that these phenotype-specific pattern maturations were associated with distinct lattice tension states. The two populations were then patterned in anisotropic rows in order to direct the cell-generated deformations and to orient global matrix remodeling. Only maturation of anisotropic fibroblast patterns, but not myofibroblasts, resulted in collagen anisotropic reorganizations both at tissue-scale, with lattice contraction, and at microscale, with embedded microbead displacements. Following a 4D bioprinting approach, LAB patterning enabled to elicit and orient the dynamic matrix remodeling mechanisms of distinct fibroblastic populations and organizations on collagen. For future studies, this method provides a new versatile tool to investigate in vitro dermal organizations and properties, processes of remodeling in healing, and new treatment opportunities.

N tau-methylhistidine release: contributions of rat skeletal muscle, GI tract, and skin

1982 ◽  
Vol 243 (4) ◽  
pp. E293-E297 ◽  
Author(s):  
S. J. Wassner ◽  
J. B. Li
Keyword(s):  
Skeletal Muscle ◽  
Gastrointestinal Tract ◽  
Soft Tissue ◽  
Fractional Catabolic Rate ◽  
Gi Tract ◽  
Rat Skeletal Muscle ◽  
Catabolic Rate ◽  
Total Body

The relative contributions of skeletal muscle, gastrointestinal tract, and skin to urinary N tau-methylhistidine (MH) excretion were estimated during in vitro studies using the rat hemicorpus preparation. After 0.5 h of perfusion, MH release into the perfusate was linear for 3 h and averaged 29.8 nmol . h-1 . 100 g hemicorpus-1. In vivo, 24-h urinary MH excretion averaged 37.3 nmol . h-1 . 100 g body wt-1. The ratio of soft tissue to skin weight is equal (3.2:1) in the whole rat and in the hemicorpus. The gastrointestinal tract released 16.0 nmol . h-1 . 100 g body wt-1 or approximately 41% of the total urinary MH excretion. Preparations perfused with or without skin showed modest differences in the rate of MH release that were not statistically significant. Skeletal muscle contains 89.8% of total body MH content, whereas gastrointestinal tract and skin contain 3.8 and 6.4%, respectively. Gastrointestinal tract actomyosin turns over rapidly with a fractional catabolic rate of 24%/day versus 1.4%/day for skeletal muscle actomyosin.

238 EFFECTS OF LEPTIN SUPPLEMENTATION ON NUCLEAR AND CYTOPLASMIC IN VITRO MATURATION OF RABBIT OOCYTES

2008 ◽  
Vol 20 (1) ◽  
pp. 198 ◽  
Author(s):  
M. Arias-Alvarez ◽  
R. M. Garcia-Garcia ◽  
L. Revuelta ◽  
P. G. Rebollar ◽  
P. L. Lorenzo
Keyword(s):  
Nutritional Status ◽  
Laser Scanning ◽  
Physiological Role ◽  
White Female ◽  
Confocal Laser ◽  
Cortical Granule ◽  
Nuclear Staining ◽  
Cytoplasmic Maturation

Reproductive function is affected substantially by nutritional status. Leptin is a peptide secreted mainly by adipocytes that reflects the amount of body fat and acts as a modulator of oocyte quality. The aim of this study was to analyze, for the first time in the rabbit, the influence of leptin on meiotic and cytoplasmic maturation (cortical granule (CG) migration) of rabbit oocytes in vitro (IVM). Cumulus–oocyte complexes (COCs) were collected from 25 young New Zealand white female rabbits (<3 parturitions) in 3 replicates. COCs were aspirated from ovarian follicles >1 mm in size and were matured in TCM-199 medium, containing sodium pyruvate, sodium bicarbonate, BSA, and 10 ng mL–1 epidermal growth factor (EGF), and supplemented with 0, 10, or 100 ng mL–1 leptin. A total of 163 COCs were treated progressively with hyaluronidase (2 mm), 0.5% pronase, 4% paraformaldehyde, 0.02% Triton X-100, and 7.5% BSA after the maturation period. Oocytes were incubated with 100 mg mL–1 fluorescein isothiocyanate (FITC)-conjugated Lens culinaris agglutinin (LCA) for CG staining and with 4′,6-diamino-2-phenylindole (DAPI) for nuclear staining, and observed under a confocal laser-scanning microscope. In addition, 17 ovulated oocytes recovered from oviducts at 20 h post- GnRH were used as in vivo-maturated controls for CG distribution. Most of the ovulated oocytes at metaphase II (MII, 100%) presented CGs located in the cortex beneath the plasma membrane (61.1 ± 11.8%). Addition of 10 ng mL–1 leptin to IVM medium significantly increased the rate of oocytes reaching MII, compared to the 0 and 100 ng mL–1 leptin concentrations (P < 0.05). The percentage of oocytes showing CG migration to the cortex was significantly increased in the 10 ng mL–1 leptin treatment group (Table 1) compared to that in the 100 ng mL–1 leptin group (P < 0.05) and tended to be higher than that in the 0 ng mL–1 leptin group (P < 0.08). The rest of the oocytes showed homogeneous CG distribution, as they were not cytoplasmic maturated. Moreover, both in vivo- and in vitro-matured oocytes had a GC-free domain overlying the MII spindle. In conclusion, addition of leptin to IVM medium at physiological dose (10 ng mL–1) improves both meiotic and cytoplasmic maturation of rabbit oocytes, whereas an excessive leptin concentration does not exert a beneficial effect. These findings suggest a physiological role for leptin in the relationship between nutritional status and regulation of oocyte maturation. Table 1. Nuclear maturation and CG distribution of oocytes after IVM This research was supported by AGL05-196 and UCM-CM research program (920249). MAA received a grant from CM and FSE. RMGG was supported by the Juan de la Cierva-MEC Program.

scholarly journals Tissue-engineered Oral Mucosa

2012 ◽  
Vol 91 (7) ◽  
pp. 642-650 ◽  
Author(s):  
K. Moharamzadeh ◽  
H. Colley ◽  
C. Murdoch ◽  
V. Hearnden ◽  
W.L. Chai ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Soft Tissue ◽  
Oral Mucosa ◽  
Dental Materials ◽  
Three Dimensional ◽  
Bacterial Invasion ◽  
Graft Material ◽  
Oral Diseases

Advances in tissue engineering have permitted the three-dimensional (3D) reconstruction of human oral mucosa for various in vivo and in vitro applications. Tissue-engineered oral mucosa have been further optimized in recent years for clinical applications as a suitable graft material for intra-oral and extra-oral repair and treatment of soft-tissue defects. Novel 3D in vitro models of oral diseases such as cancer, Candida, and bacterial invasion have been developed as alternatives to animal models for investigation of disease phenomena, their progression, and treatment, including evaluation of drug delivery systems. The introduction of 3D oral mucosal reconstructs has had a significant impact on the approaches to biocompatibility evaluation of dental materials and oral healthcare products as well as the study of implant-soft tissue interfaces. This review article discusses the recent advances in tissue engineering and applications of tissue-engineered human oral mucosa.

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