Papillary Lines Research Articles

Metabolic evaluation of sporadic papillary kidney cancer.

377 Background: Papillary kidney cancer, which occurs in 15% of patients with kidney cancer, can be aggressive and there is currently no effective form of therapy for this disease. To evaluate the metabolic characteristics of sporadic papillary kidney cancer, we have evaluated metabolic parameters of several papillary kidney cancer cell lines and available gene expression profiles. Methods: Established cell lines derived from patients with sporadic papillary kidney cancer (LABAZ, MDACC-55, HRC-86T2) and from a hereditary form of fumarate hydratase-deficient kidney cancer (UOK262) were evaluated. All sporadic lines were initially sequenced for fumarate hydratase (FH). All cell lines were metabolically profiled using the Seahorse Extracellular Flux Analyzer and further evaluated for reactive oxygen species (ROS), mitochondrial membrane potential, and glucose dependence. Finally gene expression profiles of publically available datasets of papillary and HLRCC tumors were downloaded, normalized, and analyzed. Results: Sporadic lines had no alterations in FH and metabolic analysis demonstrated normal oxygen consumption and minimal lactate production, in contrast to highly glycolytic UOK262. Also unlike UOK262, the sporadic papillary kidney cancer lines were not sensitive to glucose withdrawal, had low levels of ROS, and had normal mitochondria membrane potential. Principal component analysis (PCA) demonstrated that HLRCC tumor specimens are very different from sporadic papillary tumors at the molecular level. Conclusions: Our study of established sporadic papillary RCC and fumarate hydratase-deficient HLRCC cell line together with analysis of available gene expression profiles demonstrates that these sporadic papillary kidney cancer cell lines appear to have a distinct metabolic profile from those in the fumarate hydratase deficient kidney cancer cell line. Understanding the metabolic basis of papillary kidney cancer could provide the foundation for the development of targeted approaches to therapy for patients with this disease.

Multifaceted suppression of aggressive behavior of thyroid carcinoma by all-trans retinoic acid induced re-differentiation

Since all-trans retinoic acid (ATRA) has shown promising results in differentiation therapy, the present study was designed to investigate the effects of ATRA on thyroid carcinoma and to evaluate the effectiveness of ATRA in redifferentiation induction of thyroid carcinoma. Therefore, we investigated cell growth rate, morphological and nuclear: cytoplasmic ratio, adherent-dependent growth, response to chemotherapy drug following differentiation, T3 and T4 measurement, and critical genes expression pattern. Papillary cell line showed more growth inhibition by ATRA, in addition, mesenchymal and spindle-shape of 8305C cells changed to polygonal. Additionally, high nuclear: cytoplasmic ratio of anaplastic decreased significantly. Redifferentiation significantly suppressed the anchorage-dependent growth in the both cell lines in a dose-dependent manner, potentiated the arsenic trioxide (ATO) effects in anaplastic and papillary cell lines. Furthermore, reduction in the expression of stemness, and invasion related genes was observed in the both cell lines. Altogether, ATRA treatment could hold the aggressive behavior of thyroid carcinoma in restraint and/or potentiate the effect of chemotherapy drug ATO.

Abstract 2017: Demethylation of HIC1 gene sensitizes thyroid cancer cells to TRAIL-induced apoptosis

Abstract Gene silencing associated with aberrant methylation of promoter region CpG islands is an acquired epigenetic alteration. It serves as an alternative to genetic defects in the inactivation of tumor suppressor and other genes in human cancers. Several genes have been shown to be epigenetically inactivated in a wide range of tumors and most neoplasms show hypermethylation of one or more genes. Concurrent methylation status of the CpG islands of 24 genes were determined in 40 PTC cases and in a panel of PTC cell lines, using methylation specific PCR. Seven genes demonstrated a relatively high frequency of aberrant methylation: RASF1 (95%), HIC1 (55%), GSTP1 (26%), P14 (25%), TMS1 (24%), DCR1 (17%) and SERF (15%). Five genes (BRACA1, P15INK4B, MGMT, BLU and APC) showed a low frequency (2-6%) of methylation, and no methylation was detected for the remaining twelve genes (P16INK4A, APAF1, FANCF, FAS, MINT25, P73, MLH1, DAPK, RARB, CASP8, E-Cadherin and SOC1. Statistical analysis demonstrated that frequency of methylated and unmethylated HIC1 was significant (p <0.05). Further clinical analysis demonstrated significant association of only HIC1 methylation with: age of patients, stage of disease and expression of HIC1 IHC data (p = <0.0001, <0.0173 and < 0.0448; respectively). HIC1 has been shown to be hypermethylated in different cancers and confers bad prognosis. HIC1 is a tumor suppressor gene which encodes a transcriptional repressor with five Kruppel-like Cys2-His2 zinc fingers in the C terminus and a protein-protein interaction domain called the BTB/POZ domain at the N terminus. Analysis of BCPAP-1 and TPC1 (papillary thyroid cell lines) revealed that they are completely methylated for HIC1 gene. Treatment of methylated thyroid cell line with the methyltransferase inhibitor, 5-aza-2’deoxy-cytidine, resulted in partial demethylation and re-expression of HIC1 gene, suggesting the role of methylation in silencing of the gene. We further evaluated the role of HIC1 gene after demethylation for apoptosis. After demethylation of HIC1 gene with 5-aza-2’deoxy-cytidine we treated our PTC cell lines with increasing doses of TRAIL and evaluated its response by Annexin/PI dual staining. We found that after demethylation of HIC1 there was increase in percentage apoptosis following increasing doses of TRAIL suggesting that HIC1 gene plays a major role in inducing apoptosis in PTC. In conclusion, HIC1 methylation may be a promising molecular marker to predict patient outcome in PTC, and may be used as therapeutic demethylating target. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2017. doi:10.1158/1538-7445.AM2011-2017

Expression of embryonic stem cell marker OCT4 in human thyroid neoplasia

Current investigations suggested that thyroid carcinoma originate from individual mature thyroid follicular epithelial cells. Here we provide the evidence for a stem cell-associated model of thyroid carcinogenesis. We investigated the expression of the octamer-binding transcription factor-4 (OCT4) in human thyroid tissues. OCT4 is a POU domain–containing transcription factor encoded by Pou5f1 and functions as an important regulator in initial cell fate decisions during mammalian development. We assessed the expression of human OCT4 transcripts in 8 normal and 12 adenoma thyroid tissues, and 12 follicular, 20 papillary and 18 anaplastic thyroid carcinoma (Ca). We also investigated OCT4 expression in seven thyroid cancer cell lines. OCT4 transcripts were detected in most anaplastic carcinoma (80%), but weak or absent in normal thyroid (25%), benign thyroid adenoma (50%), follicular (33%) and papillary (30%) thyroid Ca tissues. Furthermore, OCT4 gene activity was absent in a papillary thyroid Ca cell line (B-CPAP), weak in follicular FTC-238, FTC-236, FTC-133, but strong in anaplastic 8305-C, C643, Hth74 Ca cell lines. The stem cell gene OCT4 may play a direct role and serve as a valuable new biomarker in thyroid carcinogenesis. Future research aims to provide further evidence to our hypothesis that thyroid carcinogenesis includes an involvement of pre-existing stem cells within the adult thyroid gland.

Differential Pattern of Integrin Receptor Expression in Differentiated and Anaplastic Thyroid Cancer Cell Lines

Adhesion of tumor cells to the extracellular matrix (ECM) is a crucial step for the development of metastatic disease and is mediated by specific integrin receptor molecules (IRM). The pattern of metastatic spread differs substantially among the various histotypes of thyroid cancer (TC). However, IRM have only occasionally been characterized in TC until now. IRM expression was investigated in 10 differentiated (FTC133, 236, 238, HTC, HTC TSHr, XTC, PTC4.0/4.2, TPC1, Kat5) and two anaplastic TC cell lines (ATC, C643, Hth74), primary cultures of normal thyroid tissue (Thy1,3), and thyroid cancer specimens (TCS). Expression of 16 IRM (beta1-4, beta7, alpha1-6, alphaV, alphaIIb, alphaL, alphaM, alphaX) and of four IRM heterodimers (alpha2beta1, alpha5beta1, alphaVbeta3, alphaVbeta5), was analyzed by fluorescent-activated cell sorter (FACS) and immunohistochemical staining. Thyroid tumor cell adhesion to ECM proteins and their IRM expression in response to thyrotropin (TSH) was assessed. Follicular TC cell lines presented high levels of integrins alpha2, alpha3, alpha5, beta1, beta3 and low levels of alpha1, whereas papillary lines expressed a heterogenous pattern of IRM, dominated by alpha5 and beta1. ATC mainly displayed integrins alpha2, alpha3, alpha5, alpha6, beta1 and low levels of alpha1, alpha4 and alphaV. Integrin heterodimers correlated with monomer expression. Evaluation of TCS largely confirmed these results with few exceptions, namely alpha4, alpha6, and beta3. The ability of TC cell lines to adhere to purified ECM proteins correlated with IRM expression. TSH induced TC cell adhesion in a dose-dependent fashion, despite an unchanged array of IRM expression or level of a particular IRM. Thyroid carcinoma cell lines of different histogenetic background display profoundly different patterns of IRM expression that appear to correlate with tumor aggressiveness. In vitro adhesion to ECM proteins and IRM expression concur. Finally, TSH-stimulated adhesion of thyroid tumor cell lines to ECM may not be associated with altered IRM expression.

Enhanced expression of nicotinamide N-methyltransferase in human papillary thyroid carcinoma cells.

To gain an understanding of the molecular pathogenesis of thyroid cancer, we used DNA microarray to study the expression profiles of 10 different human thyroid carcinoma cell lines. These included papillary lines BHP 2-7, BHP 7-13, BHP 10-3, BHP 18-21, NPA 87, and TPC1; anaplastic lines ARO 81-1 and DRO 90-1; follicular line WRO 82-1; and medullary line HRO 85-1. Among the genes with increased expression in the cancer cell lines, a gene coding for nicotinamide N-methyltransferase (NNMT) was identified for being highly expressed only in the papillary cell lines. NNMT catalyzes N-methylation of nicotinamide and other structurally related compounds and is highly expressed in the human liver. The results were further confirmed by semiquantitative RT-PCR and Northern blot analysis. NNMT catalytic activities were determined in all of the cells described above and in additional cell lines. Significantly higher NNMT enzyme activities were detected in eight of 10 of the papillary lines and three of six of the follicular cell lines tested. Normal thyroid tissue, thyroid primary cultures, anaplastic cancer cells, and medullary cancer cells showed no or low enzyme activity. Immunohistochemical staining for NNMT of human thyroid specimens showed strong and abundant cytoplasmic reactions in the sections of papillary carcinomas, and weak or scanty reaction in the normal thyroid tissues. These results indicate that NNMT is a potential biomarker for papillary thyroid carcinoma.

Interpapillary Lines—The Variable Part of the Human Fingerprint

The dermatoglyphic pattern of human palms and soles is individually unique and unchanging. Their prints show the course of the papillary ridges as papillary lines. Case reports and a few older studies of repeatedly taken fingerprints could, however, show that so-called interpapillary lines can develop between the papillary lines. The questions of this study were: How often do interpapillary lines occur? Can the differences between papillary and interpapillary ridges be quantified? Five-hundred and two ink prints of the palms and fingers from the archive of the Bochum Police Department were examined retrospectively. In 121 volunteers, the appearance of interpapillary lines was examined prospectively. From the later collective, the fingerprints of 13 people with interpapillary lines and nine people without were examined further by taking two silicon prints and measuring them with laser profilometry In 215 of the 502 ink prints (42.8%) interpapillary lines could be demonstrated. In those subjects younger than 20 years they were less frequently observed (34.1%) than in those above the age of 20 (51.8%). In all cases using laser profilometry the interpapillary lines could be related to a corresponding interpapillary ridge. The interpapillary ridge heights were 24.9 +/- 10.0 microm, significantly lower than the papillary ridges, which measured 59.0 +/- 19.2 microm. Interpapillary ridge widths were with 194.8 +/- 65.1 microm significantly narrower as compared to 435.5 +/- 57.4 microm in the papillary ridge. Those papillary ridges, between which interpapillary ridges were found, were significantly further apart from each other (610.5 +/- 78.9 microm) than those without interpapillary ridges (484.9 +/- 70.6 microm). During the course of a lifetime new ridges between the regular papillary ridges can develop or manifest. The fact that interpapillary lines are more frequently found on the right hands in men and those with increasing age is consistent with the theory that they correspond to degenerative changes and with sensitivity of touch.

Uterine Carcinoma With Serous and Choriocarcinomatous Differentiation

Nongestational, nongonadal, and nonteratoma-related choriocarcinoma is an extremely rare entity. The tumor may be pure or associated with carcinoma. Six cases of primary endometrial carcinomas with the presence of syncytiotrophoblastlike beta-human chorionic gonadotropin (beta-HCG)-positive cells have been reported. We describe a case of endometrial carcinoma in a postmenopausal woman, that was composed almost entirely of syncytiotrophoblastic and cytotrophoblastic elements, except in the areas of lymphatic and myometrial invasion, where the neoplasm expressed a papillary serous carcinoma conformation with numerous psammoma bodies. There was not a clear transition between choriocarcinoma and serous carcinoma components. Immunohistochemically, beta-HCG was strongly positive in trophoblastic cells, whereas papillary areas expressed epithelial membrane antigen. These results suggest a double differentiation from malignant stem cells toward an extraembryonal germinal line and a papillary epithelial line. A poor prognosis is expected for this type of neoplasm with extraembryonic differentiation. In the present case, the histologic subtype of uterine papillary serous carcinoma could be an additional risk factor.

Tamoxifen inhibits growth, migration, and invasion of human follicular and papillary thyroid cancer cells in vitro and in vivo.

Prognosis of differentiated thyroid cancer is best in young women. It has been proposed that sex steroids protect premenopausal women from aggressive thyroid malignancies. Some thyroid tissues have estrogen receptors, and estrogen stimulates human thyroid cells. Tamoxifen is thought to exert its antiproliferative effects mainly by blocking estrogen stimulation. However, recently, mechanisms independent of estrogen interactions were found to be important for the favorable effect. We investigated the effect of tamoxifen on the growth, migration, and invasion in three follicular thyroid cancer cell lines (FTC133, primary; FTC236, lymph node; and FTC238, lung metastasis) from one patient and two papillary lines (PTC-UC1 and PTC-UC3). Growth was measured by dimethylthiazol-diphenyltetrazolium bromide assays, and migration was determined by the ability of cells to penetrate 8-microns pore membranes, which were covered by Matrigel for invasion assays. For in vivo experiments, we used xenografts of FTC133 in nude mice. Tamoxifen (1.5 mumol/L) inhibited the growth of all thyroid cancer cell lines (FTC133, 59%; FTC236, 42%; FTC238, 46%; P < 0.01). This effect was less pronounced in PTC-UC1 (25%) and PTC-UC3 (19%; P < 0.006) cell lines. Tamoxifen also inhibited migration and invasion of FTC more than PTC. Invasion of FTC133 was inhibited by 36% (P < 0.01), FTC236 by 30%, and FTC238 by 32%. Immunohistochemistry showed no estrogen receptors in any cell line. Also, estradiol had no significant effect on the growth, migration, or invasion of FTC or PTC. Tamoxifen treatment inhibited the growth of FTC133 xenografts in nude mice by 52% compared to that in placebo-treated controls (P < 0.002). In conclusion, tamoxifen inhibited the growth, migration, and invasion of differentiated thyroid cancer cells in vitro and in vivo. This was not reversed by estrogen. Tamoxifen acts independently of estrogen interactions and may be useful as an adjuvant treatment for some differentiated human thyroid malignancies.

Functional and molecular evidence for Shaker-like K+ channels in rabbit renal papillary epithelial cell line.

The rabbit papillary epithelial cell line GRB-PAP1 was used to determine the ion transport characteristics of a model of the distal nephron and terminal collecting duct. When grown on permeable supports, monolayers developed a significant electrical resistance and a benzamil-sensitive short-circuit current, indicating that they had the property of electrogenic Na+ transport. Using the whole cell patch-clamp technique, we found that the dominant current in these cells was a slowly inactivating, time- and voltage-dependent K+ current. This current was activated by voltages more positive than -30 mV. At +30 mV, the peak outward currents were > 300 pA. The magnitude of the outward currents and their reversal potentials depended strongly on the extracellular concentration of K+ and not on the extracellular concentration of Cl-. These currents were inhibited by either tetraethylammonium, 4-aminopyridine, charybdotoxin, or dendrotoxin. These characteristics, together with the kinetics of activation and inactivation, are the general characteristics of delayed rectifier channels seen in many muscle and neuronal cells. Because many of these types of channels share sequence homology with the Shaker family of channels cloned from Drosophila, we sought to identify a molecular correlate. Using reverse transcription followed by polymerase chain reaction to amplify Shaker-like sequences, we cloned and sequenced a single 881-bp fragment. The sequence shared identity with a recently reported rabbit Shaker channel that belongs to the subclass Kv 1.2. These data show that this renal papillary epithelial cell line, which has the capability of electrogenic Na+ transport, expresses functional delayed rectifier channels.

Transforming growth factor-beta 1 is a negative regulator for differentiated thyroid cancer: studies of growth, migration, invasion, and adhesion of cultured follicular and papillary thyroid cancer cell lines.

Invasion and metastasis may be caused by the escape of tumor cells from the negative control of growth factors. We analyzed the effects of transforming growth factor-beta 1 (TGF beta 1) on growth, migration, invasion, and adhesion in three follicular thyroid cancer cell lines (FTC133, primary; FTC236, lymph node metastasis; FTC238, lung metastasis) from one patient and in a papillary line (PTC-UC3). Cell growth was measured by dimethylthiazol-diphenyltetrazolium bromide assays, and migration (basal or epidermal growth factor stimulated) was determined by the ability of cells to penetrate 8-microns pore membranes that were covered with Matrigel for invasion assays. Moreover, we studied tumor cell adhesion to collagen type IV, fibronectin, and laminin. TGF beta 1 inhibited growth in FTC (FTC133, by 31%; FTC236, 15%; FTC238, 17%; P < 0.008), but not in PTC. Migration was inhibited in all cell lines. TGF beta 1 inhibited epidermal growth factor-stimulated migration of FTC133 by 43% vs. 29% without epidermal growth factor (P < 0.03). TGF beta 1 also inhibited invasion (FTC133, 32%; FTC236, 18%; FTC238, 16%; PTC-UC3, 32%; P < 0.02). All cell lines adhered preferably to collagen type IV and fibronectin. TGF beta 1 enhanced adhesion. Again, these effects were less pronounced in the FTC metastases. In conclusion, TGF beta 1 inhibits the growth, migration, and invasion of thyroid cancer cells in vitro. It enhances adhesion to components of the extracellular matrix. Metastatic thyroid tumors may be less responsive to the negative regulation of TGF beta 1.

Activation of osmolyte efflux from cultured renal papillary epithelial cells

The rabbit renal papillary epithelial cell line PAP-HT25 accumulates sorbitol and other organic osmolytes when cultured in hypertonic media. When returned to isotonic media, PAP-HT25 cells swell because of water influx and then shrink to their normal volume because of rapid osmolyte and water efflux (volume regulatory decrease, VRD). Sorbitol efflux from PAP-HT25 cells during VRD was reduced to 18% of control by incubation of the cells with 100 microM eicosatetraynoic acid (ETYA), indicating that an enzyme that metabolizes arachidonic acid (AA) is a key component of the efflux process. Sorbitol efflux was unaffected by incubation with cyclooxygenase and lipoxygenase inhibitors but was reduced to 9% by incubation with 100 microM ketoconazole and to 37% by incubation with 100 microM SKF-525A, indicating that the cytochrome P-450 limb of the AA cascade is involved in the efflux process. The efflux of other organic osmolytes betaine and myoinositol, but not glycerolphosphorylcholine, was also inhibited by incubation with ETYA and ketoconazole.

Sorbitol permease: an apical membrane transporter in cultured renal papillary epithelial cells

The efflux of sorbitol from the rabbit papillary epithelial cell line PAP-HT25 occurs through a specific transport pathway, which we denote the "sorbitol permease." The permease was studied by measuring cell volume changes that accompanied osmotic swelling and by determination of the sorbitol efflux from plasma membrane vesicles. The cell volume studies showed that sorbitol efflux in response to hypotonicity occurred only across the apical membrane of the cells and that loss of sorbitol was the primary mechanism for regulatory volume decrease (RVD) by these cells. Quinidine, a permeant inhibitor of the sorbitol permease, was shown to prevent RVD when added to either apical or basolateral bathing solution. Cell volume experiments also showed that the permease was present only on the apical membrane of cells that had been grown in isotonic medium and did not accumulate sorbitol. The permease could be demonstrated in membrane vesicles obtained from cells exposed to a hypotonic environment before being homogenized. Quinidine blocked the sorbitol efflux from vesicles indicating that it either directly inhibited the permease or a membrane-associated activation step.

Qualitative aspects of palmar dermatoglyphics in a sample of Sardinian population

The author examines certain qualitative aspects of palmar dermatoglyphics in 820 individuals of both sexes from the city of Cagliari (Sardinia). The overall results obtained are discussed and the sexual and lateral differences are considered. The sample examined differs from other Mediterranean samples because of a tendency toward a vertical trend of the papillary lines, a lower frequency of patterns in the 2nd and 3rd interdigital areas and a higher frequency of patterns in the 4th interdigital area.

Dermatoglyphics of twins: a study based on a new systematics.

Summary1. The Author has investigated on a twin material of 34 twin pairs the papillary line patterns on the fingers, the interdigital areas of the palms, and the hallucal area of the soles according to a systematics accounted for by the Author in earlier works.2. The diagnosis of zygosity has been based on a comparison for the morphological particularities and on blood group analyses, in the cases in which the relative chance for dizygosity for the concordant pairs has been calculated.3. The frequency distribution for the papillary line patterns of the twin pairs showed no significant divergence with respect to the large Swedish population, earlier investigated.4. The 19 MZ twin pairs showed a concordance of 84.2-89.5% for the total qualitative value, total ridge-count and for the hallucal patterns.

Application of silver nitrate labelled with Ag 110 m for autoradiographic detection of fingerprints

It has been shown that carrier free solutions of Ag 110 m NO 3 are not suitable for detecting prints of papillary lines by autoradiographic method. But 0·01 N carrier solutions of AgNO 3 labelled with Ag 110 m having maximal specific activity 2·0–2·5 μc/ml can be used for detecting fingerprints by this method. An empirical equation was derived which gives the exact exposure time of the radioactive specimens on the photographic film to obtain the best autoradiographs. To calculate this the counting rate in cpm of a 0·1 ml portion of the solution used and the investigated specimen under the same geometrical conditions.

Detection of fingerprints by autoradiography (Initial report)

A simple autoradiographic method of detecting prints of papillary lines is described. U and Ag 110 were used as sources of radioactivity. The isotope was applied to the prints of papillary lines by sprinkling UO 2 or AgCl labelled with Ag 110 and also be depositing Ag 110 from aqueous solution of Ag 110NO 3 directly on the prints or on the prints previously exposed to iodine vapour. The subjects of these experiments included both fresh prints and prints several days old made on paper, glass and textile. The usefulness for dactyloscopic purposes of the labelled compounds which were tried was established. Further research in this subject is still in progress.

Racial differences in the papillary lines of the palm

Racial differences in the papillary lines of the palm