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PubMed2006

Recombinant antisense C-myc adenovirus increase in vitro sensitivity of osteosarcoma MG-63 cells to cisplatin.

C-myc is an oncogene with the important role of cell proliferation controller. It has been found to be amplified and overexpressed in osteosarcoma. Moreover, it can promote cell transformation and induce metastatic features. Some studies showed that overexpression of c-myc could induce resistance in response to antineoplastic agents. Currently, we constructed the recombinant adenovirus (Ad-Asc-myc) encoding antisense c-myc fragment and investigated its effect on the in vitro sensitivity of osteosarcoma MG-63 cells to cisplatin(CDDP). The osteosarcoma MG-63 cells were transfected by the Ad-Asc-myc in vitro, and Western Blot, MTT assay, RT-PCR, flow cytometry (FCM), and transmission electron microscopy (TEM) were used to study expression of c-myc and caspase-3 protein, tumor cell proliferation in vitro, cell apoptotic morphology and cell cycle change. Ad-Asc-myc encoding antisense c-myc fragment was obtained with the titer of 2.0 x 10(9) pfu/ml. Ad-Asc-myc downregulated the expression of c-myc protein after transfected MG-63 cells for 48 hours, combined with the treatment of 2.0, 5.0 microg/ml cisplatin for 2 hours can inhibited tumor cells proliferation in vitro by 33.4 and 54.2 percent, respectively, which had significant difference compared with control recombinant adenovirus (Ad-LacZ) groups (P < 0.05). RT-PCR revealed that Ad-Asc-myc downregulated expression of bcl-2 and upregulated expression of Bax, and no appreciable changes were observed in the expression of E2F-1. Detection of caspase-3 protein TEM, and FCM analysis showed that Ad-Asc-myc could induce apoptosis of transfected cells, which was enhanced by the treatment of cisplatin. Cell cycle analysis showed that obvious G(2)/M phase arrested in transfected cells. In conclusion, Ad-Asc-myc increased the in vitro sensitivity of osteosarcoma MG-63 cells to cisplatin as well as induced apoptosis.

Adenoviridae↗

PubMed2006

Stable CpG hypomethylation of adipogenic promoters in freshly isolated, cultured, and differentiated mesenchymal stem cells from adipose tissue.

Mesenchymal stem cells from adipose tissue can differentiate into mesodermal lineages. Differentiation potential, however, varies between clones of adipose stem cells (ASCs), raising the hypothesis that epigenetic differences account for this variability. We report here a bisulfite sequencing analysis of CpG methylation of adipogenic (leptin [LEP], peroxisome proliferator-activated receptor gamma 2 [PPARG2], fatty acid-binding protein 4 [FABP4], and lipoprotein lipase [LPL]) promoters and of nonadipogenic (myogenin [MYOG], CD31, and GAPDH) loci in freshly isolated human ASCs and in cultured ASCs, in relation to gene expression and differentiation potential. Uncultured ASCs display hypomethylated adipogenic promoters, in contrast to myogenic and endothelial loci, which are methylated. Adipogenic promoters exhibit mosaic CpG methylation, on the basis of heterogeneous methylation between cells and of variation in the extent of methylation of a given CpG between donors, and both between and within clonal cell lines. DNA methylation reflects neither transcriptional status nor potential for gene expression upon differentiation. ASC culture preserves hypomethylation of adipogenic promoters; however, between- and within-clone mosaic methylation is detected. Adipogenic differentiation also maintains the overall CpG hypomethylation of LEP, PPARG2, FABP4, and LPL despite demethylation of specific CpGs and transcriptional induction. Furthermore, enhanced methylation at adipogenic loci in primary differentiated cells unrelated to adipogenesis argues for ASC specificity of the hypomethylated state of these loci. Therefore, mosaic hypomethylation of adipogenic promoters may constitute a molecular signature of ASCs, and DNA methylation does not seem to be a determinant of differentiation potential of these cells.

Adipogenesis↗

PubMed1992

Adenosquamous carcinoma of the lung. Clinicopathologic and immunohistochemical features.

Adenosquamous carcinomas (ASC) of the lung comprise only 1.8% of all pulmonary cancers. Eleven patients with this disease (6 men and 5 women; mean age, 62 years [range, 51 to 78 years]) were treated. On the basis of pathologic and immunohistochemical evidence, the tumors were separated into three groups: five ASCs of predominantly glandular type, which may originate from squamous metaplasia in a preexisting adenocarcinoma; three mixed type ASCs, possibly derived from the transition of undifferentiated carcinoma to two different elements; and three predominantly squamous type ASCs resembling high-grade muco-epidermoid carcinoma. The 5-year survival rate of 35% for patients with ASCs was the same as that for patients with other nonsmall cell carcinomas. For two patients with ASCs of the predominantly glandular type and for one with the mixed type, resection was incomplete because of extensive local disease. All tumors of the predominantly squamous type could be excised completely. However, differences in the malignant potential of these three types of ASCs are still controversial.

Adenocarcinoma↗

PubMed2006

Ascorbate acts as a highly potent inducer of chromate mutagenesis and clastogenesis: linkage to DNA breaks in G2 phase by mismatch repair.

Here we examined the role of cellular vitamin C in genotoxicity of carcinogenic chromium(VI) that requires reduction to induce DNA damage. In the presence of ascorbate (Asc), low 0.2-2 microM doses of Cr(VI) caused 10-15 times more chromosomal breakage in primary human bronchial epithelial cells or lung fibroblasts. DNA double-strand breaks (DSB) were preferentially generated in G2 phase as detected by colocalization of H2AX and 53BP1 foci in cyclin B1-expressing cells. Asc dramatically increased the formation of centromere-negative micronuclei, demonstrating that induced DSB were inefficiently repaired. DSB in G2 cells were caused by aberrant mismatch repair of Cr damage in replicated DNA, as DNA polymerase inhibitor aphidicolin and silencing of MSH2 or MLH1 by shRNA suppressed induction of H2AX and micronuclei. Cr(VI) was also up to 10 times more mutagenic in cells containing Asc. Increasing Asc concentrations generated progressively more mutations and DSB, revealing the genotoxic potential of otherwise nontoxic Cr(VI) doses. Asc amplified genotoxicity of Cr(VI) by altering the spectrum of DNA damage, as total Cr-DNA binding was unchanged and post-Cr loading of Asc exhibited no effects. Collectively, these studies demonstrated that Asc-dependent metabolism is the main source of genotoxic and mutagenic damage in Cr(VI)-exposed cells.

Ascorbic Acid↗

PubMed2005

Immunocytochemical expression of p16INK4A and Ki-67 in cytologically negative and equivocal pap smears positive for oncogenic human papillomavirus.

This study was designed to analyze the cross-sectional comparison of the p16 and Ki-67 immunocytochemical expression in negative and equivocal (atypical squamous cells of undetermined significance (ASC-US)) liquid-based cytology (LBC) samples testing positive for high-risk human papillomavirus (HPV) types with HC2 assay or polymerase-chain reaction (PCR). A series of 199 consecutive LBC specimens derived from the same number of women participating in the ongoing Latin American Screening Study at Leonor Mendes de Barros Hospital, Sao Paulo, were analyzed using immunocytochemistry for expression of p16 and Ki-67 in negative and equivocal LBC samples testing positive for high-risk HPV types with hybrid capture II test (HC2) or PCR. All patients with at least one test positive (cytology, PCR, and/or HC2) were followed each 6 months for 3 years. The follow-up procedure consisted of visual examination, colposcopic inspection, cytology, and HC2 assay. Among the negative cytologic samples, 101 were HPV-positive and 55 HPV-negative. Of the HPV-positive group, 59 of 101 cases (58.4%) were positive for both p16 and Ki67 immunostaining, and 17 of 101 (16.8%) were negative for both. The proportion of Ki-67-positivity increased almost in parallel with the increasing grade of p16-positivity (p = 0.0001 for linear trend). In the HPV-negative group, both markers were negative in 41 of 55 cases (74.5%), and no statistical relationship was observed between the two markers (Pearson, p = 0.595). HPV-positive ASC-US samples demonstrated a simultaneous positive immunoreaction for p16 and Ki67 in 11 of 16 cases (68.7%), whereas 3 (18.7%) were concurrently negative. The relationship between the two markers was of borderline significance (Pearson, p = 0.053), but no linear relationship was found between the graded p16 and Ki-67 expression (p = 0.065 for linear trend). In the HPV-negative ASC-US group, there was no statistical association between the graded p16 and Ki-67 positivity (Pearson, p = 0.281). After 36 months of follow-up of the ASC-US patients, 6 women still displayed ASC-US smear, of which 4 of 6 were HPV-positive and expressed both p16 and Ki-67 markers. Two of 43 ASC-US smears had high-grade squamous intraepithelial lesions diagnosed (4.6%), and 1 had low-grade squamous intraepithelial lesion (2.3%). All of those were positive for HPV, p16 and Ki-67. Patients with ASC-US diagnosis and positive high-risk HPV status and positive for p16 Ki67 should be carefully observed to exclude occurrence of a squamous intraepithelial lesion. The combination of these two markers can be a useful implement for management of women with equivocal cytology.

Biomarkers, Tumor↗

PubMed2004

Localization of an ascorbate-reducible cytochrome b561 in the plant tonoplast.

As a free radical scavenger, and cofactor, ascorbate (ASC) is a key player in the regulation of cellular redox processes. It is involved in responses to biotic and abiotic stresses and in the control of enzyme activities and metabolic reactions. Cytochromes (Cyts) b561 catalyze ASC-driven trans-membrane electron transport and contribute to ASC-mediated redox reactions in subcellular compartments. Putative Cyts b561 have been identified in Arabidopsis (ecotype Columbia) on the basis of sequence similarity to their mammalian counterparts. However, little is known about the function or subcellular localization of this unique class of membrane proteins. We have expressed one of the putative Arabidopsis Cyt b561 genes (CYBASC1) in yeast and we demonstrate that this protein encodes an ASC-reducible b-type Cyt with absorbance characteristics similar to that of other members of this family. Several lines of independent evidence demonstrate that CYBASC1 is localized at the plant tonoplast (TO). Isoform-specific antibodies against CYBASC1 indicate that this protein cosediments with the TO marker on sucrose gradients. Moreover, CYBASC1 is strongly enriched in TO-enriched membrane fractions, and TO fractions contain an ASC-reducible b-type Cyt with alpha-band absorbance maximum near 561 nm. The TO ASC-reducible Cyt has a high specific activity, suggesting that it is a major constituent of this membrane. These results provide evidence for the presence of trans-membrane redox components in this membrane type, and they suggest the coupling of cytoplasmic and vacuolar metabolic reactions through ASC-mediated redox activity.

Arabidopsis↗

PubMed2004

The ascorbic acid redox state controls guard cell signaling and stomatal movement.

H(2)O(2) serves an important stress signaling function and promotes stomatal closure, whereas ascorbic acid (Asc) is the major antioxidant that scavenges H(2)O(2). Dehydroascorbate reductase (DHAR) catalyzes the reduction of dehydroascorbate (oxidized ascorbate) to Asc and thus contributes to the regulation of the Asc redox state. In this study, we observed that the level of H(2)O(2) and the Asc redox state in guard cells and whole leaves are diurnally regulated such that the former increases during the afternoon, whereas the latter decreases. Plants with an increased guard cell Asc redox state were generated by increasing DHAR expression, and these exhibited a reduction in the level of guard cell H(2)O(2). In addition, a higher percentage of open stomata, an increase in total open stomatal area, increased stomatal conductance, and increased transpiration were observed. Guard cells with an increase in Asc redox state were less responsive to H(2)O(2) or abscisic acid signaling, and the plants exhibited greater water loss under drought conditions, whereas suppressing DHAR expression conferred increased drought tolerance. Our analyses suggest that DHAR serves to maintain a basal level of Asc recycling in guard cells that is insufficient to scavenge the high rate of H(2)O(2) produced in the afternoon, thus resulting in stomatal closure.

Ascorbic Acid↗

PubMed1993

The B cell repertoire of patients with rheumatoid arthritis. Frequencies and specificities of peripheral blood B cells reacting with human IgG, human collagens, a mycobacterial heat shock protein and other antigens.

Using a potent in vitro limiting dilution culture system, we have activated human peripheral blood B cells to proliferate and to differentiate into antibody-secreting cells (ASC). Under these conditions 25-100% of B cells are clonally expanded and produce IgM, IgG or IgA. Culture supernatants were tested for antibodies binding to human IgG-Fc fragments (RF), the 65-kD heat shock protein of Mycobacterium bovis (hsp60), human collagens type I, II, IV, V, transferrin, lactoferrin, albumins, and gelatine. All blood samples contained precursors of ASC (p-ASC) able to produce IgM binding to these antigens in frequencies above 0.03% of B cells. Most interestingly, a significant difference exists between rheumatoid arthritis (RA) patients and controls, concerning the relative frequencies of p-ASC able to produce monospecific or multireactive RF. Whereas most p-ASC(RF) in RA patients are monospecific (mean ratio 3.7), most p-ASC(RF) in healthy control persons are cross-reactive with at least one of five other antigens tested (mean ratio 0.2). The data suggest a disease-specific expansion of p-ASC committed to the production of monospecific rheumatoid factors.

Antibody Formation↗

PubMed1995

Anti-malaria antibody-producing B cell frequencies in adults after a Plasmodium falciparum outbreak in Madagascar.

The central highlands of Madagascar offer a unique opportunity to explore the malaria immune memory, as the last murderous epidemic in the study area occurred 8 years ago. Quantification of the circulating memory B lymphocytes reacting to Plasmodium falciparum was assessed among 14 Madagascans by using a limiting dilution assay, applied to the EL4 culture system, which leads to activation, proliferation and differentiation into antibody-secreting cells (ASC) of most peripheral B cells. This system allowed us to observe, without any malaria-specific restimulation, a geometric mean frequency of one anti-P. falciparum ASC among 2992 circulating B cells, except for one Madagascan who did not have any detectable ASC. A geometric mean frequency of one anti-P. falciparum ASC among 1403 was obtained for six malaria hyperimmune Cameroonians, but conversely, no anti-malaria ASC was detected in the blood of six malaria non-immune French control subjects. Anti-P. falciparum ASC frequencies and serum specific antibodies were strongly related. Our results indicate that anti-malaria ASC are still present in peripheral blood of Madagascan subjects, who have not been exposed to P. falciparum for several years. These responder B cells reflect the malaria B cell memory acquired during the last epidemic.

Adult↗

PubMed1991

Immune response to prolonged intestinal exposure to antigen.

The influence of prolonged intestinal antigen exposure on the immune response in humans was investigated. Two groups of volunteers were vaccinated orally with live Salmonella typhi Ty21a given in enteric-coated capsules three (group 3 x E) or six (group 6 x E) at 2-day intervals. The immune response was followed for 1 month by enumerating the antibody-secreting cells (ASC) in the peripheral blood. Soon after vaccination specific ASC were observed in the blood of all volunteers. In group 3 x E, the response peaked on day 5 or 7 and had faded away by day 14. In group 6 x E, by contrast, there was no clear single peak of the response, and the ASC numbers were high in several consecutive measurements. On day 14, considerable numbers of ASC were still detected in all cases; the responses had mostly faded away by day 22. These results show that prolonged exposure to antigen in the intestine induces a prolonged response of specific ASC in peripheral blood. This is an important prerequisite for the application of the ASC assay to study mucosal infections, in which the actual time of onset is often unknown. In addition, the findings suggest that the ASC assay might offer new possibilities for assessing the persistence of microbial antigens in infections.

Adolescent↗

PubMedDate not supplied

Analyses of atypical squamous cells refined by the 2001 Bethesda System: the distribution and clinical significance of follow-up management.

This study was conducted to analyze the clinical significance of follow-up diagnostic methods of atypical squamous cells (ASC) (the 2001 Bethesda System) cases according to age. A computerized search of the cytology database was performed to retrieve all cases diagnosed as ASC from 2001 to 2003. The pathologic reports for all follow-up diagnoses were reviewed. We divided the patients into two groups according to their age, younger than 50 years of age and 50 years and older, and follow-up diagnoses were compared between the two groups. ASC was identified in 1035 (2.0%) of 49,882 women screened, and a total of 914 patients were eligible. In atypical squamous cells of undetermined significance (ASC-US) cases, colposcopically directed biopsy showed CIN I (CIN is cervical intraepithelial neoplasia) or higher grade lesions in 34.9% of cases younger than 50 years of age and in 17.4% of cases 50 years and older (P= 0.000). However, repeat Pap smears and human papillomavirus DNA testing showed no differences between the two groups. In contrast, the three methods did not exhibit significant difference between the two groups in patients with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) (P= 0.743). Colposcopically directed biopsy for the ASC-US was more useful in patients younger than 50 years of age than in those who were 50 years and older. It is suggested that age should be considered in deciding follow-up diagnostic methods in patients with ASC-US.

Adult↗

PubMed2002

TGFbeta induces morphological and molecular changes similar to human anterior subcapsular cataract.

BACKGROUND: Transforming growth factor beta (TGFbeta) has been shown to induce subcapsular plaques in cultured rat lenses as well as in lenses of transgenic mice. In the present study the authors have extended their analysis of these cataract models to determine how closely they mimic human cataract. In particular, they studied the maturation of cataract in the transgenic model to determine if it develops similar features as previously described for anterior subcapsular cataract (ASC) in humans. Furthermore, they investigated whether both of these animal models express the range of molecular markers that have now been shown to be present in human ASC. METHODS: Histology and periodic acid Schiff staining were used to study the development and maturation of subcapsular plaques in transgenic mice overexpressing TGFbeta1 in the lens. Immunolabelling methods were used to identify the molecular markers for ASC in both the transgenic mouse model and in rat lenses cultured with TGFbeta2. RESULTS: Histological analysis showed that the subcapsular plaques that develop in adult transgenic mouse lenses bear a striking similarity to mature human ASC, including the formation of a new epithelial-like layer extending between the subcapsular plaque and the underlying fibre mass. All known molecular markers for human ASC were induced in both rodent models, including collagen types I and III, tenascin, and fibronectin. They also identified the presence of desmin in these plaques, a putative novel marker for human cataract. CONCLUSIONS: In both transgenic mouse and rat lens culture models TGFbeta induces markers similar to those found in human ASC. Atypical expression of these cataract markers is also characteristic of posterior capsular opacification (PCO). The molecular markers expressed are typical of a myofibroblastic/fibroblastic phenotype and suggest that a common feature of ASC and PCO may be induction of an epithelial-mesenchymal transition by TGFbeta.

Animals↗

PubMed2005

Immortal DNA strand cosegregation requires p53/IMPDH-dependent asymmetric self-renewal associated with adult stem cells.

Because they are long-lived and cycle continuously, adult stem cells (ASCs) are predicted as the most common precursor for cancers in adult mammalian tissues. Two unique attributes have been proposed to restrict the carcinogenic potential of ASCs. These are asymmetric self-renewal that limits their number and immortal DNA strand cosegregation that limits their accumulation of mutations due to DNA replication errors. Until recently, the molecular basis and regulation of these important ASC-specific functions were unknown. We developed engineered cultured cells that exhibit asymmetric self-renewal and immortal DNA strand cosegregation. These model cells were used to show that both ASC-specific functions are regulated by the p53 cancer gene. Previously, we proposed that IMP dehydrogenase (IMPDH) was an essential factor for p53-dependent asymmetric self-renewal. We now confirm this proposal and provide quantitative evidence that asymmetric self-renewal is acutely sensitive to even modest changes in IMPDH expression. These analyses reveal that immortal DNA strand cosegregation is also regulated by IMPDH and confirm the original implicit precept that immortal DNA strand cosegregation is specific to cells undergoing asymmetric self-renewal (i.e., ASCs). With IMPDH being the rate-determining enzyme for guanine ribonucleotide (rGNP) biosynthesis, its requirement implicates rGNPs as important regulators of ASC asymmetric self-renewal and immortal DNA strand cosegregation. An in silico analysis of global gene expression data from human cancer cell lines underscored the importance of p53-IMPDH-rGNP regulation for normal tissue cell kinetics, providing further support for the concept that ASCs are key targets for adult tissue carcinogenesis.

Cell Cycle↗

PubMed2005

Adenosquamous carcinoma of the pancreas.

BACKGROUND/AIMS: Adenosquamous carcinoma (ASC) of the pancreas is rare and correct preoperative diagnosis is difficult. Case reports of ASC of the pancreas are sporadic and have typically employed small series. This study investigated the clinicopathological features of 7 cases of ASC of the pancreas and reviewed the pertinent literature to elucidate this rare disease. METHODOLOGY: Seven patients (4 men and 3 women; age range 38-79 years; median 66 years) with ASC of the pancreas who underwent surgical treatment at Chang Gung Memorial Hospital between February 1993 and April 2000 were retrospectively reviewed. RESULTS: Symptoms of ASC were as follows: abdominal pain (85.7%), body weight loss (85.7%), jaundice (42.9%) and anorexia (42.9%). The tumors were located at the head of the pancreas in 4 patients (57.1%), at the body in 2, and at the tail in 2. One patient had ASC at the body and tail. Most cases (5/7, 71.4%) were anemic. Seven (100%) and 5 patients (71.4%) had elevated serum CEA and CA19-9 levels, respectively. Curative pancreaticoduodenectomy was performed on 2 patients, bypass surgery on 3, and exploratory laparotomy on 2. Two patients underwent intraoperative radiotherapy. Three patients received postoperative adjuvant chemotherapy. No surgical mortality or morbidity occurred. Five of 7 patients (71.4%) died within 6 months after surgery. The median survival of the 7 patients was 4.41 months (range 1.12-22.42). CONCLUSIONS: Patients with ASC present symptoms similar to those of adenocarcinoma of the pancreas. Most patients had dismal prognosis despite aggressive surgery with or without adjuvant therapy.

Adult↗

PubMed2004

Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells.

BACKGROUND: The delivery of autologous cells to increase angiogenesis is emerging as a treatment option for patients with cardiovascular disease but may be limited by the accessibility of sufficient cell numbers. The beneficial effects of delivered cells appear to be related to their pluripotency and ability to secrete growth factors. We examined nonadipocyte stromal cells from human subcutaneous fat as a novel source of therapeutic cells. METHODS AND RESULTS: Adipose stromal cells (ASCs) were isolated from human subcutaneous adipose tissue and characterized by flow cytometry. ASCs secreted 1203+/-254 pg of vascular endothelial growth factor (VEGF) per 10(6) cells, 12 280+/-2944 pg of hepatocyte growth factor per 10(6) cells, and 1247+/-346 pg of transforming growth factor-beta per 10(6) cells. When ASCs were cultured in hypoxic conditions, VEGF secretion increased 5-fold to 5980+/-1066 pg/10(6) cells (P=0.0016). The secretion of VEGF could also be augmented 200-fold by transfection of ASCs with a plasmid encoding VEGF (P<0.05). Conditioned media obtained from hypoxic ASCs significantly increased endothelial cell growth (P<0.001) and reduced endothelial cell apoptosis (P<0.05). Nude mice with ischemic hindlimbs demonstrated marked perfusion improvement when treated with human ASCs (P<0.05). CONCLUSIONS: Our experiments delineate the angiogenic and antiapoptotic potential of easily accessible subcutaneous adipose stromal cells by demonstrating the secretion of multiple potentially synergistic proangiogenic growth factors. These findings suggest that autologous delivery of either native or transduced subcutaneous ASCs, which are regulated by hypoxia, may be a novel therapeutic option to enhance angiogenesis or achieve cardiovascular protection.

Adipose Tissue↗

PubMed2001

Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2.

ASC-2 is a recently isolated transcriptional cointegrator molecule, which is amplified in human cancers and stimulates transactivation by nuclear receptors, AP-1, nuclear factor kappaB (NFkappaB), serum response factor (SRF), and numerous other transcription factors. ASC-2 contained two nuclear receptor-interaction domains, both of which are dependent on the integrity of their core LXXLL sequences. Surprisingly, the C-terminal LXXLL motif specifically interacted with oxysterol receptor LXRss, whereas the N-terminal motif bound a broad range of nuclear receptors. These interactions appeared to be essential because a specific subregion of ASC-2 including the N- or C-terminal LXXLL motif acted as a potent dominant negative mutant with transactivation by appropriate nuclear receptors. In addition, the autonomous transactivation domain (AD) of ASC-2 was found to consist of three separable subregions; i.e. AD1, AD2, and AD3. In particular, AD2 and AD3 were binding sites for CREB binding protein (CBP), and CBP-neutralizing E1A repressed the autonomous transactivation function of ASC-2. Furthermore, the receptor transactivation was not enhanced by ASC-2 in the presence of E1A and significantly impaired by overexpressed AD2. From these results, we concluded that ASC-2 directly binds to nuclear receptors and recruits CBP to mediate the nuclear receptor transactivation in vivo.

Amino Acid Sequence↗

PubMed2006

Clinical significance of cytologic diagnosis of atypical squamous cells, cannot exclude high grade, in perimenopausal and postmenopausal women.

We used cytohistologic correlation to determine the clinical significance of atypical squamous cells, cannot exclude high grade (ASC-H) in perimenopausal and postmenopausal women. A computer search identified 250 Papanicolaou smears from women older than 45 years with a diagnosis of ASC- H. Cases were considered perimenopausal (45 to < 55 years; 150 cases) and postmenopausal ((3)55 years; 100 cases). No follow-up data were available for 33 cases, which were excluded. The remaining 217 cases (perimenopausal, 127; postmenopausal, 90) had surgical or cytologic follow-up. Results of follow-up colposcopic biopsy were available for 176 (81.1%) and cytology for 41 (18.9%) women. Follow-up results were as follows: perimenopausal women, negative, 50 (39.4%); mild dysplasia (low-grade squamous intraepithelial lesion [LSIL]), 46 (36.2%); high-grade dysplasia (high-grade SIL [HSIL]); 28 (22.0%); and ASC of undetermined significance (ASC-US), 3 (2.4%); postmenopausal women, negative, 52 (58%); LSIL, 31 (34%); HSIL, 5 (6%); and ASC-US, 2 (2%). The diagnosis of ASC-H in postmenopausal women usually is associated with LSIL or a negative diagnosis on follow-up, suggesting a less aggressive surveillance and treatment regimen is needed for postmenopausal women with ASC-H.

Aged↗

PubMed2006

Adult stem and transit-amplifying cell location.

Adult stem cells (ASC)--able to self renew and to intervene in maintaining the structural and functional integrity of their original tissue--can express greater plasticity than traditionally attributed to them, adopting functional phenotypes and expression profiles of cells from other tissues. Therefore, they could be useful to regenerative medicine and tissue engineering. Transit-amplifying cells (TAC) are committed progenitors among the ASC and their terminally differentiated daughter cells. The ASC reside in a specialized physical location named niche, which constitutes a three-dimensional microenviroment where ASC and TAC are protected and controlled in their self-renewing capacity and differentiation. The niche can be located near or far from the recruitment point, requiring a short or long-distance cellular migration, respectively. This paper briefly reviews the current status of research about ASC plasticity, transdifferentiation, fusion and functional adaptation mechanisms. Subsequently, ASC and TAC occurrence, characteristics and location have been considered in the skin, cornea, respiratory tract, teeth, gastrointestinal tract, liver, pancreas, salivary glands, kidney, breast, prostate, endometrium, mesenchyma, bone marrow, skeletal and cardiac muscle, nervous system and pituitary gland. Moreover, the role of cancer ASC has also been revised.

Animals↗