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At least 127 records · Page 7Linked to original sources

Well-differentiated epithelial thyroid cancer management in the Asia Pacific region: a report and clinical practice guideline.

CONTEXT: Thyroid cancer is among the 10 most common malignancies in populations in the Asia Pacific region, where access to various relevant health care resources varies widely. OBJECTIVE: An expert consensus conference was held to define regional patterns of practice and guidelines for optimal management of well-differentiated epithelial thyroid carcinomas. RESULTS: Practice patterns vary from country to country, as would be anticipated form their variety of ethnic and racial populations, health care systems, economies, and cultures. Thyroid cancer care is provided by a number of medical and surgical specialists, usually including endocrinologists. The thyroid surgical skills, experience, and outcomes vary widely in the region. Radioiodine is available, to a greater or lesser extent, is almost all countries. Laboratory services for thyroid function monitoring are universally accessible; thyroglobulin assays are available in most countries. Recombinant thyrotropin is approved for use in only two countries, but can be accessed in some others on a "named patient" compassionate need basis. Access to advanced imaging, for exampke, positron emission tomography (PET) scanning, is limited to a few countries. CONCLUSIONS: In light of these realities, appropriate strategies for initial treatment and postoperative monitoring of patients with thyroid cancer have been defined, and these are presented and discussed.

Female↗

Resveratrol induces colon tumor cell apoptosis independently of p53 and precede by epithelial differentiation, mitochondrial proliferation and membrane potential collapse.

Resveratrol, a polyphenol present in wine and grapes, can inhibit tumor cell growth in vitro and tumorigenesis in vivo. Some of its effects have been linked to activation of the p53 tumor suppressor; however, p53 is frequently mutated in tumors, particularly in the common and often therapy-resistant colon cancers. Using the human wild-type p53-expressing HCT116 colon carcinoma cell line and HCT116 cells with both p53 alleles inactivated by homologous recombination, we show in the current study that resveratrol at concentrations comparable to those found in some foods can induce apoptosis independently of p53. The cell death is primarily mitochondria-mediated and not receptor-mediated. No cells survived in cultures continuously exposed to 100 microM resveratrol for 120 hr. When compared with 5-FU, resveratrol stimulated p53 accumulation and activity only weakly and with delayed kinetics and neither the increased levels nor the activity affected apoptosis detectably. The apoptosis agonist Bax was overproduced in response to resveratrol regardless of p53 status, yet the kinetics of Bax expression were influenced by p53. Remarkably, apoptosis was preceded by mitochondrial proliferation and signs of epithelial differentiation. Thus, resveratrol triggers a p53-independent apoptotic pathway in HCT116 cells that may be linked to differentiation.

Antineoplastic Agents, Phytogenic↗

A case of recurrent intramural uterine stromal tumor with epithelial differentiation effectively treated with oral low-dose administration of etoposide.

A 66-year-old woman was diagnosed as having myoma of the uterus and total hysterectomy with bilateral salpingo-oophorectomy was performed. The histopathological findings were puzzling, and the case was finally diagnosed as intramural uterine stromal tumor with epithelial differentiation. Three years after the operation, a firm tumor developed in the pelvic cavity. Laparotomy failed to remove the tumor and neither CAP (cyclophosphamide 500 mg, adriamycin 50 mg, CDDP 70 mg) therapy nor radiation therapy was effective. Oral administration of etoposide (25 mg/day), however, showed PR (50% decrease) as determined by CT scanning, and ultrasonography, and no metastatic lesions were found. This tumor was coincident with the endometrial stromal tumor with epithelial elements classified by Clement and Scully. The histological feature of the tumors and the efficacy of oral etoposide therapy are discussed in this study.

Administration, Oral↗

A case of intramural uterine stromal tumor with epithelial differentiation.

A case of intrauterine tumor in a 62-year-old Japanese woman is presented. It was thought initially that this was a case of uterine tumor resembling an ovarian sex cord tumor. To examine the cytological features of the tumor cells, electron microscopical and immunohistochemical studies were done, and a hormone assay of the tumor tissue was performed. The tumor cells were rich in rough endoplasmic reticulum (rER), mitochondria and microfilaments. Some tumor cells tended to form glandular patterns, but these epithelial elements were frequently scattered among fibrous stromal elements. Though many tumor cells with an epithelial appearance possessed a large quantity of cytokeratin and vimentin, they did not secrete estradiol, progesterone, testosterone or human chorionic gonadotropin. This case was finally diagnosed as an intramural uterine stromal tumor with epithelial differentiation after taking all the available data into consideration. This would be classified as an endometrial stromal tumor with epithelial elements, recently proposed and named by Clement and Scully.

Antigens, Neoplasm↗

Glandular cardiac myxomas. Histologic, immunohistochemical, and ultrastructural evidence of epithelial differentiation.

Histologic, histochemical, immunocytochemical, and ultrastructural features of two cardiac myxomas containing glandular elements are reported. Glandular elements in both cases stained positively with both mucicarmine and periodic acid-Schiff reagent with diastase pretreatment (DPAS). Immunoperoxidase studies demonstrated positivity of the glandular cells for carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and keratin. Factor VIII-related antigen (FVIIIAg) was identified only in cells lining vascular spaces. Electron microscopic study of one tumor demonstrated well-formed glands having basement membranes, junctional complexes, and apical secretory granules. These findings indicate the capacity for true epithelial differentiation of cardiac myxomas and have implications both as regards the histologic diagnosis of these tumors and their histogenesis.

Adult↗

Induction of epithelial differentiation and DNA demethylation in hamster malignant oral keratinocyte by ornithine decarboxylase antizyme.

The hamster ornithine decarboxylase antizyme (ODC-Az) cDNA was transfected into the hamster malignant oral keratinocyte cell line, HCPC-1. Ectopic expression of ODC-Az resulted in the reversion of malignant phenotypes and alteration of DNA methylation status of CCGG sites. The phenotypes examined include ODC enzymatic activity, doubling time, morphological change, anchorage dependent growth, tumorigenicity in nude mice, induction of epithelial differentiation marker protein (involucrin), and change of cell cycle position. Comparison of CCGG DNA methylation status of the ODC-Az and control vector transfectants revealed a significant increase in demethylation of 5-methyl cytosines (m5C) of CCGG sites in the ODC-Az transfectants. Ectopic expression of ODC-Az gene in hamster malignant oral keratinocytes led to reduce ODC activity and the subsequent demethylation of 5-methyl cytosines, presumably via the ODC/ polyamines/ decarboxylated S-adenosylmethionine (dc-AdoMet) pathways. Our data suggest that ODC-Az shared the same pathway of polyamines/ dc-AdoMet/DNA methyltransferase (DNA MTase). We propose that ODC-Az mediates a novel mechanism in tumor suppression by DNA demethylation and presumably re-activation of key cellular genes silenced by DNA hypermethylation during cancer development. Oncogene (2001) 20, 24 - 33.

Agar↗

Monoclonal antibodies recognize a cell surface marker of epithelial differentiation in the rabbit reproductive tract.

Monoclonal antibodies against the cell surface were produced by immunizing mice with endometrial scrapings prepared from 6-day pregnant rabbits. Spleen cells from an immune mouse were fused with myeloma cells and cultured by standard hybridoma technology methods. Hybridoma supernatants were screened for reaction with the apical epithelial surface by immunohistochemistry on frozen sections of uterus from 6-day pregnant rabbits, and positive colonies were cloned by limiting dilution. Ascites fluid was produced in mice from hybridoma clones that gave a consistent pattern of apical epithelial surface staining through 6 sub-clonings. Antibodies in the ascites fluid were tested by immunohistochemistry on frozen sections of uterus, oviduct, lung, liver and kidney from nonpregnant or 6-day pregnant rabbits. At a dilution of 1:5000, the antibodies recognized an antigen that was specific to the apical surface of luminal but not glandular epithelium of the 6-day pregnant uterus and could not be detected in the nonpregnant uterine epithelium. At higher concentrations of antibody (1:100 to 1:1000), crossreaction was seen with antigens in stromal and myometrial cells of pregnant and nonpregnant uterus. At a dilution of 1:5000, the antibody also crossreacted with some components of lung, liver and kidney but without discriminating between the two reproductive states. In the oviduct, staining of the surface epithelium was specific to the pregnant state. We conclude that this monoclonal antibody has a high affinity for a luminal epithelial cell surface antigen in the reproductive tract of the pregnant rabbit and shows multiple organ reactivity with other tissues that is not affected by pregnancy. This antigen will provide a useful cell surface marker of epithelial differentiation in the progestational reproductive tract.

Animals↗

MSX2 promotes vaginal epithelial differentiation and wolffian duct regression and dampens the vaginal response to diethylstilbestrol.

In utero exposure to diethylstilbestrol (DES) leads to patterning defects in the female reproductive tract (FRT) and a propensity to the development of vaginal adenocarcinomas in humans. In the mouse, DES treatment similarly induces a plethora of FRT developmental defects, including stratification of uterine epithelium and presence of glandular tissue in cervix and vagina. Uterine abnormalities are associated with repression of the homeobox gene Msx2, and DES leads to an altered uterine response in Msx2 mutants including a dilated uterine lumen. Here we investigate the role of Msx2 in normal vaginal development and in FRT response to DES. During vaginal development, Msx2 is required for Tgfbeta2 and Tgfbeta3 expression and for proper vaginal epithelial differentiation. Moreover, Msx2 is involved in caudal Wolffian duct regression by promoting apoptosis. Consistently, neonatal DES exposure represses Msx2 expression in the Wolffian duct epithelium and inhibits its apoptosis and subsequent regression. Intriguingly, although DES treatment also represses Msx2 expression in the vaginal epithelium, a much more severe DES-induced vaginal phenotype was observed in Msx2 mutant mice, including a complete failure of Müllerian vaginal epithelial stratification and a severely dilated vaginal lumen, accompanied by loss of p63 and water channel protein expression. These results demonstrate a critical role for Msx2 in counteracting the effect of DES on FRT patterning and suggest that the response to DES may be highly variable depending on the genotype of an individual.

Animals↗

The epithelial differentiating activity in vivo of (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylenyl) -1-propenyl]benzoic acid and 4,4-difluororetinoic acid.

Female rats fed on a vitamin A-deficient diet from weaning were oophorectomized after introitus and used to test analogues of all-trans-retinoic acid for epithelial differentiation activity by the vaginal-smear assay. Several modifications have been made in the assay; housing facilities were modified, the diet changed and the existing scoring system for the assay altered. The arotinoid (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylenyl)-1 -propenyl] benzoic acid was 12-fold more active than all-trans-retinoic acid, which had a 50% effective dose (ED50) of 80 pmol/vagina. The fluorinated analogue 4,4-difluororetinoic acid had an ED50 of 2.5 nmol/vagina and was therefore 30-fold less active than all-trans-retinoic acid.

Animals↗

A comparison of the susceptibility of three human gut tumour-derived differentiated epithelial cell lines, primary monkey kidney cells and human rhabdomyosarcoma cell line to 66-prototype strains of human enteroviruses.

The growth of prototype strains of 31 serotypes of ECHO, 3 polio, 6 Coxsackie B, 24 Coxsackie A and enterovirus serotypes 70 and 71 were tested in parallel in primary monkey kidney cells (PMK), RD cells and three gut tumour-derived differentiated epithelial cell lines (HRT-18 HT-29 in SKCO-1). All 31 serotypes of ECHO viruses grew in HT-29, 27 and SKCO-1, 5 in HRT-18, 29 in PMK and 29 in RD. There was good growth of poliovirus serotypes in all five cell types. Coxsackie B viruses grew well in all the cell lines except RD. Fifteen of the Coxsackie A viruses grew in SKCO-1, 4 in HT-29, 3 in HRT-18 and 7 in RD. Enterovirus serotypes 70 and 71 grew only in RD cells after 3 serial passages. These results showed that 2 of the gut tumour-derived cell lines, HT-29 and SKCO-1 had a markedly wider susceptibility, with comparable or wider sensitivity, for enteroviruses, than PMK and RD. While their use for field isolation from clinical samples is not yet fully established HT-29 and SKCO-1 would appear to be ideal for a variety of laboratory manipulations of the majority of enteroviruses.

Animals↗

Malignant rhabdoid tumor of the liver. Evidence for epithelial differentiation.

Malignant rhabdoid tumors most commonly occur in the kidney. Rarely does this tumor arise in extrarenal sites; a single documented primary hepatic tumor has been described. We describe two patients who had malignant tumors arising in the liver. These tumors demonstrated cytologic, histologic, and ultrastructural features typical of malignant rhabdoid tumor. By immunohistochemistry, the tumor cells from both patients expressed the epithelial membrane antigen, cytokeratin, and vimentin and cells from one patient contained alpha 1-antitrypsin. Neither patient had evidence of renal involvement at autopsy. Thus, we demonstrate that this rapidly fatal tumor contains cells showing features of epithelial differentiation, and that it may occur as a primary hepatic tumor.

Female↗

Spatial and temporal expression pattern of a novel gene in the frog Xenopus laevis: correlations with adult intestinal epithelial differentiation during metamorphosis.

We report the cloning of a novel gene (ID14) and its expression pattern in tadpoles and adults of Xenopus laevis. ID14 encodes a 315-amino acid protein that has a signal peptide and a nidogen domain. Even though several genes have a nidogen domain, ID14 is not the homolog of any known gene. ID14 is a late thyroid hormone (TH)-regulated gene in the tadpole intestine, and its expression in the intestine does not begin until the climax of metamorphosis, correlating with adult intestinal epithelial differentiation. In contrast, ID14 is expressed in tadpole skin and tail and is not regulated by TH. In situ hybridization revealed that this putative extracellular matrix protein is expressed in the epithelia of the tadpole skin and tail and in the intestinal epithelium after metamorphosis. In the adult, ID14 is found predominantly in the intestine with weak expression in the stomach, lung, and testis. Its exclusive expression in the adult intestinal epithelial cells makes it a useful marker for developmental studies and may give insights into cell/cell interactions in intestinal metamorphosis and adult intestinal stem cell maintenance.

Amino Acid Sequence↗

Distinctive expression of filaggrin and trichohyalin during various pathways of epithelial differentiation.

Filaggrin and trichohyalin are keratin intermediate filament-associated proteins, and are primarily expressed in the granular cells of the epidermis and in the inner root sheath cells of the hair follicles, respectively. These two proteins are, however, occasionally co-expressed in some tissues. To gain more insights into the mechanisms for expression and processing of (pro)filaggrin and trichohyalin during various pathways of epithelial differentiation, we compared their localization by double immunostaining techniques in normal and psoriatic epidermis, tongue filiform papillae and cultured human epidermal keratinocytes. In normal foreskin, trichohyalin immunoreactive cells were observed only occasionally and, when present, they always co-expressed filaggrin. Trichohyalin expression occurred, however, in filaggrin-negative cells as well as in filaggrin-positive cells in the psoriatic epidermis, tongue papillae and cultured keratinocytes. Filaggrin and trichohyalin were induced independently at different times following calcium shift in cultured keratinocytes. Immunoelectron microscopy demonstrated the distinct intracellular distribution of filaggrin and trichohyalin. Some filaggrin granules were observed in the cells where trichohyalin was diffusely distributed. Likewise some trichohyalin granules were found in the cells with diffuse filaggrin labelling. These results suggest the existence of distinct expression/processing mechanisms of filaggrin and trichohyalin in differentiating keratinocytes.

Adult↗

Regulatory sequences of the mouse villin gene that efficiently drive transgenic expression in immature and differentiated epithelial cells of small and large intestines.

Villin is an early marker of epithelial cells from the digestive and urogenital tracts. Indeed villin is expressed in the stem cells and the proliferative cells of the intestinal crypts. To investigate the underlying molecular mechanisms and particularly those responsible for the restricted tissue specificity, a large genomic region of the mouse villin gene has been analyzed. A 9-kilobase (kb) regulatory region of the mouse villin gene (harboring 3.5 kb upstream the transcription start site and 5.5 kb of the first intron) was able to promote transcription of the LacZ reporter gene in the small and large intestines of transgenic mice, in a transmissible manner, and thus efficiently directed subsequent beta-galactosidase expression in epithelial cells along the entire crypt-villus axis. In the kidney, the transgene was also expressed in the epithelial cells of the proximal tubules but is likely sensitive to the site of integration. A construct lacking the first intron restricted beta-galactosidase expression to the small intestine. Thus, the 9-kb genomic region contains the necessary cis-acting elements to recapitulate the tissue-specific expression pattern of the endogenous villin gene. Hence, these regulatory sequences can be used to target heterologous genes in immature and differentiated epithelial cells of the small and/or large intestinal mucosa.

Animals↗

Primary retroperitoneal mucinous cystadenomas with gastric epithelial differentiation.

We present two rare cases of retroperitoneal mucinous cystadenomas (RMC) by clinical data, light microscopy, electron microscopy, histochemistry, and immunohistochemistry. Both tumors occurred in women. We excluded attachment to any organ. Additional immunohistochemical examinations were performed for comparison in 10 cases of ovarian mucinous cystadenomas (OMC). Both RMC showed no significant immunohistochemical differences from the OMC. Ultrastructurally and histologically the RMC resemble OMC reported in the literature. Immunohistologically, we proved gastric epithelial differentiation by using one monoclonal antibody (2B5) recognizing gastric mucin and one polyclonal antibody against pepsinogen II (PG II). In spite of this, the histogenesis of RMC in the presented cases in the end remains uncertain.

Adult↗

Hormonal modification of epithelial differentiation and expression of cell surface heparan sulfate proteoglycan in the mouse vaginal epithelium. An immunohistochemical and electron microscopic study.

Immunohistochemical staining of a cell surface antigen was evaluated in the adult mouse vaginal epithelium at different stages of the estrous cycle and in response to exogenous sex hormones and endocrine ablation. The antigen is recognized by a monoclonal antibody directed against the core protein of a heparan sulfate-rich proteoglycan from mouse mammary epithelial cells. Vaginal epithelium at estrus showed the most intense staining; cells of the basal and intermediate layers stained, but the more superficial parakeratotic, cornified, and sloughing layers did not. At metestrus and diestrus, immunostaining was limited to basal cells and some deeper intermediate cells. The staining was absent from the more superficial layers which were invaded by leukocytes. At late diestrus and proestrus, staining was primarily in the intermediate cells; staining was absent from parakeratotic and basal cell layers. There was no staining of submucosal cells throughout the estrous cycle. In ovariectomized mice, staining of the epithelium was reduced in intensity. Diethylstilbestrol treatment of ovariectomized mice increased the intensity and extent of epithelial staining and produced a state comparable to that seen at estrous. Administration of a combination of progesterone and estradiol to ovariectomized mice elicited vaginal stratification and mucification, a state comparable to that observed in diestrus in which basal and intermediate layers stained while the apical mucified cells did not. In animals expressing natural or diethylstilbestrol-induced estrus, electron microscopic immunoperoxidase staining revealed the presence of the antigen on the surface of cell processes in the intercellular spaces between vaginal epithelial cells. Cuprolinic blue staining for glycosaminoglycan using the critical electrolyte concentration method demonstrated filamentous structures on the epithelial surface in the same location to that of the antigen. The stained filaments were reduced by treatment with heparitinase, but not with chondroitinase ABC or heparin, suggesting that they contained heparan sulfate glycosaminoglycan. These data suggest that as vaginal epithelial differentiation fluctuates during the estrous cycle in response to changing levels of estrogens and progesterone, expression of a cell surface heparan sulfate proteoglycan undergoes dramatic changes spatially and quantitatively.

Animals↗

Epithelial differentiation and taste buds in the soft palate of the monkey, Macaca irus.

A combination of light, transmission and scanning electron microscopy was employed to demonstrate the occurrence, arrangement and structure of taste buds in the oral mucosa of the soft palate of monkeys (Macaca irus). Taste buds are found in aggregates confined to 0.15 to 0.3 mm wide, round islands of keratinizing epithelium embedded in the normally non-keratinizing integument. Topography, configuration and structure of these epithelial islands and their taste buds are described, and the question of a developmental and functional interrelationship between epithelial differentiation and properties, and taste bud function is discussed.

Animals↗

Testicular stromal tumor: ultrastructural, immunohistochemical, and gel electrophoretic evidence of epithelial differentiation.

A testicular tumor, removed from a 52-year-old man, was composed of uniform spindle cells and abundant interposed collagen, and was histologically diagnosed as a stromal tumor. Electron microscopy revealed cords of cells sometimes surrounded by a basal lamina. Desmosome-like junctions were found between some cells, and immunostaining for desmoplakins was positive. Immunofluorescence studies also showed cytokeratin-positivity in most and vimentin-positivity in some of the tumor cells. The presence of typical simple epithelial cytokeratins of Mr 40000, 45000 and 52000 was revealed by the western blotting method. Cytokeratin positivity in the tumor cells suggests the epithelial nature of this mesenchymal-looking tumor. The tumor might arise from cytokeratin-positive epithelial elements of the testis or its covering mesothelium, but the histogenesis remains unresolved. Our findings suggest that some of the so-called testicular stromal tumors may in fact be of epithelial nature by presenting features typical of epithelial differentiation.

Cell Differentiation↗