Actual Proliferating Index and p53 protein expression as prognostic marker in odontogenic cysts.

PubMed

Gadbail, A R; Chaudhary, M; Patil, S; Gawande, M

2009-10-01

The purpose of this study was to evaluate the biological aggressiveness of odontogenic keratocyst/keratocystic odontogenic tumour (KCOT), radicular cyst (RC) and dentigerous cyst (DC) by observing the actual proliferative activity of epithelium, and p53 protein expression. The actual proliferative activity was measured by Ki-67 Labelling Index and argyrophilic nucleolar organizing regions (AgNOR) count per nucleus. The p53 protein expression was also evaluated. Ki-67 positive cells were observed higher in suprabasal cell layers of KCOT with uniform distribution, a few of them were predominantly observed in basal cell layer in RC and DC. The AgNOR count was significantly higher in suprabasal cell layers of KCOT. The actual proliferative activity was noted to be higher in suprabasal cell layers of KCOT. The p53 immunolabelling was dense and scattered in basal and suprabasal cell layers in KCOT. The weakly stained p53 positive cells were observed diffusely distributed in KCOT, whereas they were mainly seen in basal cell layer of RC and DC. The quantitative and qualitative differences of the proliferative activity and the p53 protein expression in sporadic KCOT may be associated with intrinsic growth potential that could play a role in its development and explain locally aggressive biological behaviour. AgNOR count and p53 protein detection in odontogenic lesions can be of great consequence to predict the biological behaviour and prognosis.

Cell surface marker profiling of human tracheal basal cells reveals distinct subpopulations, identifies MST1/MSP as a mitogenic signal, and identifies new biomarkers for lung squamous cell carcinomas.

PubMed

Van de Laar, Emily; Clifford, Monica; Hasenoeder, Stefan; Kim, Bo Ram; Wang, Dennis; Lee, Sharon; Paterson, Josh; Vu, Nancy M; Waddell, Thomas K; Keshavjee, Shaf; Tsao, Ming-Sound; Ailles, Laurie; Moghal, Nadeem

2014-12-31

The large airways of the lungs (trachea and bronchi) are lined with a pseudostratified mucociliary epithelium, which is maintained by stem cells/progenitors within the basal cell compartment. Alterations in basal cell behavior can contribute to large airway diseases including squamous cell carcinomas (SQCCs). Basal cells have traditionally been thought of as a uniform population defined by basolateral position, cuboidal cell shape, and expression of pan-basal cell lineage markers like KRT5 and TP63. While some evidence suggests that basal cells are not all functionally equivalent, few heterogeneously expressed markers have been identified to purify and study subpopulations. In addition, few signaling pathways have been identified that regulate their cell behavior. The goals of this work were to investigate tracheal basal cell diversity and to identify new signaling pathways that regulate basal cell behavior. We used flow cytometry (FACS) to profile cell surface marker expression at a single cell level in primary human tracheal basal cell cultures that maintain stem cell/progenitor activity. FACS results were validated with tissue staining, in silico comparisons with normal basal cell and lung cancer datasets, and an in vitro proliferation assay. We identified 105 surface markers, with 47 markers identifying potential subpopulations. These subpopulations generally fell into more (~ > 13%) or less abundant (~ < 6%) groups. Microarray gene expression profiling supported the heterogeneous expression of these markers in the total population, and immunostaining of large airway tissue suggested that some of these markers are relevant in vivo. 24 markers were enriched in lung SQCCs relative to adenocarcinomas, with four markers having prognostic significance in SQCCs. We also identified 33 signaling receptors, including the MST1R/RON growth factor receptor, whose ligand MST1/MSP was mitogenic for basal cells. This work provides the largest description to date of molecular diversity among human large airway basal cells. Furthermore, these markers can be used to further study basal cell function in repair and disease, and may aid in the classification and study of SQCCs.

Transforming growth factor-β signaling: emerging stem cell target in metastatic breast cancer?

PubMed Central

Tan, Antoinette R.; Alexe, Gabriela; Reiss, Michael

2009-01-01

In most human breast cancers, lowering of TGFβ receptor- or Smad gene expression combined with increased levels of TGFβs in the tumor microenvironment is sufficient to abrogate TGFβs tumor suppressive effects and to induce a mesenchymal, motile and invasive phenotype. In genetic mouse models, TGFβ signaling suppresses de novo mammary cancer formation but promotes metastasis of tumors that have broken through TGFβ tumor suppression. In mouse models of “triple-negative” or basal-like breast cancer, treatment with TGFβ neutralizing anti-bodies or receptor kinase inhibitors strongly inhibits development of lung- and bone metastases. These TGFβ antagonists do not significantly affect tumor cell proliferation or apoptosis. Rather, they de-repress anti-tumor immunity, inhibit angiogenesis and reverse the mesenchymal, motile, invasive phenotype characteristic of basal-like and HER2-positive breast cancer cells. Patterns of TGFβ target genes upregulation in human breast cancers suggest that TGFβ may drive tumor progression in estrogen-independent cancer, while it mediates a suppressive host cell response in estrogen-dependent luminal cancers. In addition, TGFβ appears to play a key role in maintaining the mammary epithelial (cancer) stem cell pool, in part by inducing a mesenchymal phenotype, while differentiated, estrogen receptor-positive, luminal cells are unresponsive to TGFβ because the TGFBR2 receptor gene is transcriptionally silent. These same cells respond to estrogen by downregulating TGFβ, while antiestrogens act by upregulating TGFβ. This model predicts that inhibiting TGFβ signaling should drive the differentiation of mammary stem cells into ductal cells. Consequently, TGFβ antagonists may convert basal-like or HER2-positive cancers to a more epithelioid, non-proliferating (and, perhaps, non-metastatic) phenotype. Conversely, these agents might antagonize the therapeutic effects of anti-estrogens in estrogen-dependent luminal cancers. These predictions need to be addressed prospectively in clinical trials and should inform the selection of patient populations most likely to benefit from this novel anti-metastatic therapeutic approach. PMID:18841463

A novel form of epithelial wound healing of the embryonic epidermis.

PubMed

Armstrong, Margaret T; Turlo, Kirsten; Elges, Chris J; Dayton, Sarah M; Lee, Janet; Armstrong, Peter B

2006-08-01

The embryonic epidermis of amniotes is a two-cell layer sheet with a periderm positioned superficial to the basal cell layer which, itself, attaches apically to the basal surface of the periderm and basally to the basal lamina. The presence of the periderm is essential to maintain the basal layer as a two-dimensional monolayer. Wounds to the epidermis that remove selectively just the periderm are healed by a stacking of the basal layer cells that constitute the wound bed. Basal cell stacking involves the desertion of the basal lamina by many of the cells so as to increase their contact area with other basal layer cells. This suggests that a preferential adhesion to the planar basal lamina is not important for the monolayered organization of the basal layer but, instead, association with inner surface of the planar periderm is the principal process that maintains the basal layer as a monolayer. The conversion of the basal layer from monolayer to multilayer during wound healing diminishes its planar area, resulting in movement of the wound borders toward the center of the wound. This is a novel scenario for wound healing.

How Are Squamous and Basal Cell Skin Cancers Diagnosed?

MedlinePlus

... and Staging Tests for Basal and Squamous Cell Skin Cancers Most skin cancers are brought to a doctor’s ... Skin Cancers? More In Basal and Squamous Cell Skin Cancer About Basal and Squamous Cell Skin Cancer Causes, ...

Luminal epithelial cells within the mammary gland can produce basal cells upon oncogenic stress.

PubMed

Hein, S M; Haricharan, S; Johnston, A N; Toneff, M J; Reddy, J P; Dong, J; Bu, W; Li, Y

2016-03-17

In the normal mammary gland, the basal epithelium is known to be bipotent and can generate either basal or luminal cells, whereas the luminal epithelium has not been demonstrated to contribute to the basal compartment in an intact and normally developed mammary gland. It is not clear whether cellular heterogeneity within a breast tumor results from transformation of bipotent basal cells or from transformation and subsequent basal conversion of the more differentiated luminal cells. Here we used a retroviral vector to express an oncogene specifically in a small number of the mammary luminal epithelial cells and tested their potential to produce basal cells during tumorigenesis. This in-vivo lineage-tracing work demonstrates that luminal cells are capable of producing basal cells on activation of either polyoma middle T antigen or ErbB2 signaling. These findings reveal the plasticity of the luminal compartment during tumorigenesis and provide an explanation for cellular heterogeneity within a cancer.

Luminal Epithelial Cells within the Mammary Gland Can Produce Basal Cells upon Oncogenic Stress

PubMed Central

Hein, Sarah M.; Haricharan, Svasti; Johnston, Alyssa N.; Toneff, Michael J.; Reddy, Jay P.; Dong, Jie; Bu, Wen; Li, Yi

2015-01-01

In the normal mammary gland, the basal epithelium is known to be bi-potent and can generate either basal or luminal cells, whereas the luminal epithelium has not been demonstrated to contribute to the basal compartment in an intact and normally developed mammary gland. It is not clear whether cellular heterogeneity within a breast tumor results from transformation of bi-potent basal cells or from transformation and subsequent basal conversion of the more differentiated luminal cells. Here, we used a retroviral vector to express an oncogene specifically in a small number of the mammary luminal epithelial cells and tested their potential to produce basal cells during tumorigenesis. This in vivo lineage tracing work demonstrates that luminal cells are capable of producing basal cells upon activation of either Polyoma Middle T antigen (PyMT) or ErbB2 signaling. These findings reveal the plasticity of the luminal compartment during tumorigenesis and provide an explanation for cellular heterogeneity within a cancer. PMID:26096929

Differentiation of anchoring junctions in tracheal basal cells in the growing rat.

PubMed

Evans, M J; Cox, R A; Burke, A S; Moller, P C

1992-02-01

A function of airway basal cells is to attach ciliated and nonciliated columnar cells to the basal lamina. The significance of the basal cell in attachment is related to the height of the columnar epithelium. In taller epithelia, basal cells are more numerous and differentiated with respect to anchoring junctional adhesion mechanisms (desmosomes, hemidesmosomes, and the cytoskeleton) than in shorter epithelia. In this study, we determined if basal cell anchoring junctional adhesion mechanisms differentiated during growth of the airway. Tracheas from five 3-day-old, five 30-day-old, and five 90-day-old rats were prepared for electron microscopy and morphometrically studied by standard techniques. The circumference of the trachea increased from 2.5 +/- 0.2 to 7.5 +/- 0.4 mm during growth. The height of the columnar cell increased from 13.4 +/- 1.5 to 24.6 +/- 3.9 microns, and the number of basal cells per millimeter increased from 3.2 +/- 0.7 to 9.6 +/- 1.8 during growth. The number of desmosomes per basal cell profile increased significantly from 1.5 +/- 0.1 to 2.1 +/- 0.1, as did keratin filament volume density from 0.046 +/- 0.05 to 0.098 +/- 0.032. The amount of hemidesmosome attachment per basal cell did not increase significantly during growth of the airway. These data demonstrate that as tracheas grow in circumference, the columnar cells increase in height, basal cells increase in number, and anchoring junctional adhesion mechanisms differentiate in the basal cells. These changes are closely related to the height of the epithelium and result in maintaining a constant amount of attachment between the columnar epithelium and the basal lamina as the epithelium increases in height.

Direct Demonstration of a Growth-Induced Water Potential Gradient.

PubMed

Nonami, H.; Boyer, J. S.

1993-05-01

When transpiration is negligible, water potentials in growing tissues are less than those in mature tissues and have been predicted to form gradients that move water into the enlarging cells. To determine directly whether the gradients exist, we measured water potentials along the radius of stems of intact soybean (Glycine max [L.] Merr.) seedlings growing in vermiculite in a water-saturated atmosphere. The measurements were made in individual cells by first determining the turgor with a miniature pressure probe, then determining the osmotic potential of solution from the same cell, and finally summing the two potentials. The osmotic potentials were corrected for sample mixing in the probe. The measurements were checked with a thermocouple psychrometer that gave average tissue water potentials. In the elongating region, the water potential was highest near the xylem and lowest near the epidermis and in the center of the pith. In the basal, more mature region of the same stems, water potentials were near zero next to the xylem and throughout the tissue. These basal potentials reflected mostly the potential of the xylem, which extended into the elongating tissues. Thus, the high basal potential confirmed the high potential near the xylem in the elongating tissues. The psychrometer measurements for each tissue gave average potentials that agreed with the average of the cell potentials from the pressure probe. We conclude that a radial gradient was present in the elongating region that formed a water potential field in three dimensions around the xylem and that confirmed the predictions of Molz and Boyer (F.J. Molz and J.S. Boyer [1978] Plant Physiol 62: 423-429).

Direct Demonstration of a Growth-Induced Water Potential Gradient.

PubMed Central

Nonami, H.; Boyer, J. S.

1993-01-01

When transpiration is negligible, water potentials in growing tissues are less than those in mature tissues and have been predicted to form gradients that move water into the enlarging cells. To determine directly whether the gradients exist, we measured water potentials along the radius of stems of intact soybean (Glycine max [L.] Merr.) seedlings growing in vermiculite in a water-saturated atmosphere. The measurements were made in individual cells by first determining the turgor with a miniature pressure probe, then determining the osmotic potential of solution from the same cell, and finally summing the two potentials. The osmotic potentials were corrected for sample mixing in the probe. The measurements were checked with a thermocouple psychrometer that gave average tissue water potentials. In the elongating region, the water potential was highest near the xylem and lowest near the epidermis and in the center of the pith. In the basal, more mature region of the same stems, water potentials were near zero next to the xylem and throughout the tissue. These basal potentials reflected mostly the potential of the xylem, which extended into the elongating tissues. Thus, the high basal potential confirmed the high potential near the xylem in the elongating tissues. The psychrometer measurements for each tissue gave average potentials that agreed with the average of the cell potentials from the pressure probe. We conclude that a radial gradient was present in the elongating region that formed a water potential field in three dimensions around the xylem and that confirmed the predictions of Molz and Boyer (F.J. Molz and J.S. Boyer [1978] Plant Physiol 62: 423-429). PMID:12231794

High Proliferation Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Early Breast Cancer

PubMed Central

Lluch, Ana; Ribelles, Nuria; Anton-Torres, Antonio; Sanchez-Rovira, Pedro; Albanell, Joan; Calvo, Lourdes; García-Asenjo, Jose Antonio Lopez; Palacios, Jose; Chacon, Jose Ignacio; Ruiz, Amparo; De la Haba-Rodriguez, Juan; Segui-Palmer, Miguel A.; Cirauqui, Beatriz; Margeli, Mireia; Plazaola, Arrate; Barnadas, Agusti; Casas, Maribel; Caballero, Rosalia; Carrasco, Eva; Rojo, Federico

2016-01-01

Background. In the neoadjuvant setting, changes in the proliferation marker Ki67 are associated with primary endocrine treatment efficacy, but its value as a predictor of response to chemotherapy is still controversial. Patients and Methods. We analyzed 262 patients with centralized basal Ki67 immunohistochemical evaluation derived from 4 GEICAM (Spanish Breast Cancer Group) clinical trials of neoadjuvant chemotherapy for breast cancer. The objective was to identify the optimal threshold for Ki67 using the receiver-operating characteristic curve method to maximize its predictive value for chemotherapy benefit. We also evaluated the predictive role of the defined Ki67 cutoffs for molecular subtypes defined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). Results. A basal Ki67 cutpoint of 50% predicted pathological complete response (pCR). Patients with Ki67 >50% achieved a pCR rate of 40% (36 of 91) versus a pCR rate of 19% in patients with Ki67 ≤50% (33 of 171) (p = .0004). Ki67 predictive value was especially relevant in ER-HER2− and ER-HER2+ patients (pCR rates of 42% and 64%, respectively, in patients with Ki67 >50% versus 15% and 45%, respectively, in patients with Ki67 ≤50%; p = .0337 and .3238, respectively). Both multivariate analyses confirmed the independent predictive value of the Ki67 cutpoint of 50%. Conclusion. Basal Ki67 proliferation index >50% should be considered an independent predictive factor for pCR reached after neoadjuvant chemotherapy, suggesting that cell proliferation is a phenomenon closely related to chemosensitivity. These findings could help to identify a group of patients with a potentially favorable long-term prognosis. Implications for Practice: The use of basal Ki67 status as a predictive factor of chemotherapy benefit could facilitate the identification of a patient subpopulation with high probability of achieving pathological complete response when treated with primary chemotherapy, and thus with a potentially favorable long-term prognosis. PMID:26786263

The role of basal cells in adhesion of columnar epithelium to airway basement membrane.

PubMed

Evans, M J; Plopper, C G

1988-08-01

In this report, we present a new concept of the role of the basal cell in airway epithelium. Previously, the basal cell was thought to be the progenitor cell for the columnar epithelium. However, several studies have shown that this concept may not be correct. The morphologic aspects of the basal cell suggest that it could play a role in adhesion of the columnar epithelium to the basement membrane. Basal cells form attachments with columnar cells (desmosomes) and with the basement membrane (hemidesmosomes). Columnar cells do not form hemidesmosome attachments with the basement membrane. Basal cells could strengthen the adhesion of columnar cells to the basement membrane by forming hemidesmosome attachments to the basement membrane and desmosome attachments with adjacent columnar cells. Incidental evidence from 2 existing publications concerning airway microanatomy support this concept. As columnar cells grow taller, the proportion of the cell surface in contact with the basement membrane becomes progressively smaller, and thus the cell surface area related to adhesion also becomes smaller. It was found that the number of basal cells per millimeter of basement membrane was closely related to the height of the columnar cell epithelium (r = 0.98), but not to the number of columnar cells (r = 0.42). The consistency of the relationship between increased columnar cell height (and thus decreased surface area for adhesion) and the number of basal cells present (r = 0.98) supports the concept that the basal cell plays a role in adhesion of columnar cells to the basement membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Structural centrosome aberrations sensitize polarized epithelia to basal cell extrusion.

PubMed

Ganier, Olivier; Schnerch, Dominik; Nigg, Erich A

2018-06-01

Centrosome aberrations disrupt tissue architecture and may confer invasive properties to cancer cells. Here we show that structural centrosome aberrations, induced by overexpression of either Ninein-like protein (NLP) or CEP131/AZI1, sensitize polarized mammalian epithelia to basal cell extrusion. While unperturbed epithelia typically dispose of damaged cells through apical dissemination into luminal cavities, certain oncogenic mutations cause a switch in directionality towards basal cell extrusion, raising the potential for metastatic cell dissemination. Here we report that NLP-induced centrosome aberrations trigger the preferential extrusion of damaged cells towards the basal surface of epithelial monolayers. This switch in directionality from apical to basal dissemination coincides with a profound reorganization of the microtubule cytoskeleton, which in turn prevents the contractile ring repositioning that is required to support extrusion towards the apical surface. While the basal extrusion of cells harbouring NLP-induced centrosome aberrations requires exogenously induced cell damage, structural centrosome aberrations induced by excess CEP131 trigger the spontaneous dissemination of dying cells towards the basal surface from MDCK cysts. Thus, similar to oncogenic mutations, structural centrosome aberrations can favour basal extrusion of damaged cells from polarized epithelia. Assuming that additional mutations may promote cell survival, this process could sensitize epithelia to disseminate potentially metastatic cells. © 2018 The Authors.

Aging is associated with an expansion of CD49fhi mammary stem cells that show a decline in function and increased transformation potential

PubMed Central

Dong, Qiaoxiang; Gao, Hui; Shi, Yuanshuo; Zhang, Fuchuang; Gu, Xiang; Wu, Anqi; Wang, Danhan; Chen, Yuanhong; Bandyopadhyay, Abhik; Yeh, I-Tien; Daniel, Benjamin J.; Chen, Yidong; Zou, Yi; Rebel, Vivienne L.; Walter, Christi A.; Lu, Jianxin; Huang, Changjiang; Sun, Lu-Zhe

2016-01-01

Breast cancer incidence increases during aging, yet the mechanism of age-associated mammary tumorigenesis is unclear. Mammary stem cells are believed to play an important role in breast tumorigenesis, but how their function changes with age is unknown. We compared mammary epithelial cells isolated from young and old mammary glands of different cohorts of C57BL6/J and BALB/c mice, and our findings revealed that old mammary glands were characterized by increased basal cell pool comprised of mostly CD49fhi cells, altered luminal-to-basal cell ratio, and irregular ductal morphology. More interestingly, basal stem cells in old mice were increased in frequency, but showed a functional decline of differentiation and increased neoplastic transformation potential. Gene signature enrichment analysis revealed a significant enrichment of a luminal cell gene expression signature in the basal stem cell-enriched population from old mice, suggesting some luminal cells were expressing basal markers. Immunofluorescence staining confirmed the presence of luminal cells with high CD49f expression in hyperplastic lesions implicating these cells as undergoing luminal to basal phenotypic changes during aging. Whole transcriptome analysis showed elevated immune and inflammatory responses in old basal stem cells and stromal cells, which may be the underlying cause for increased CD49fhi basal-like cells in aged glands. PMID:27852980

Aging is associated with an expansion of CD49fhi mammary stem cells that show a decline in function and increased transformation potential.

PubMed

Dong, Qiaoxiang; Gao, Hui; Shi, Yuanshuo; Zhang, Fuchuang; Gu, Xiang; Wu, Anqi; Wang, Danhan; Chen, Yuanhong; Bandyopadhyay, Abhik; Yeh, I-Tien; Daniel, Benjamin J; Chen, Yidong; Zou, Yi; Rebel, Vivienne L; Walter, Christi A; Lu, Jianxin; Huang, Changjiang; Sun, Lu-Zhe

2016-11-15

Breast cancer incidence increases during aging, yet the mechanism of age-associated mammary tumorigenesis is unclear. Mammary stem cells are believed to play an important role in breast tumorigenesis, but how their function changes with age is unknown. We compared mammary epithelial cells isolated from young and old mammary glands of different cohorts of C57BL6/J and BALB/c mice, and our findings revealed that old mammary glands were characterized by increased basal cell pool comprised of mostly CD49f hi cells, altered luminal-to-basal cell ratio, and irregular ductal morphology. More interestingly, basal stem cells in old mice were increased in frequency, but showed a functional decline of differentiation and increased neoplastic transformation potential. Gene signature enrichment analysis revealed a significant enrichment of a luminal cell gene expression signature in the basal stem cell-enriched population from old mice, suggesting some luminal cells were expressing basal markers. Immunofluorescence staining confirmed the presence of luminal cells with high CD49f expression in hyperplastic lesions implicating these cells as undergoing luminal to basal phenotypic changes during aging. Whole transcriptome analysis showed elevated immune and inflammatory responses in old basal stem cells and stromal cells, which may be the underlying cause for increased CD49f hi basal-like cells in aged glands.

Red Dot Basal Cell Carcinoma: Report of Cases and Review of This Unique Presentation of Basal Cell Carcinoma.

PubMed

Cohen, Philip R

2017-03-22

Red dot basal cell carcinoma is a unique variant of basal cell carcinoma. Including the three patients described in this report, red dot basal cell carcinoma has only been described in seven individuals. This paper describes the features of two males and one female with red dot basal cell carcinoma and reviews the characteristics of other patients with this clinical subtype of basal cell carcinoma. A 70-year-old male developed a pearly-colored papule with a red dot in the center on his nasal tip. A 71-year-old male developed a red dot surrounded by a flesh-colored papule on his left nostril. Lastly, a 74-year-old female developed a red dot within an area of erythema on her left mid back. Biopsy of the lesions all showed nodular and/or superficial basal cell carcinoma. Correlation of the clinical presentation and pathology established the diagnosis of red dot basal cell carcinoma. The tumors were treated by excision using the Mohs surgical technique. Pubmed was searched with the keyword: basal, cell, cancer, carcinoma, dot, red, and skin. The papers generated by the search and their references were reviewed. Red dot basal cell carcinoma has been described in three females and two males; the gender was not reported in two patients. The tumor was located on the nose (five patients), back (one patient) and thigh (one patient). Cancer presented as a solitary small red macule or papule; often, the carcinoma was surrounded by erythema or a flesh-colored papule. Although basal cell carcinomas usually do not blanch after a glass microscope slide is pressed against them, the red dot basal cell carcinoma blanched after diascopy in two of the patients, resulting in a delay of diagnosis in one of these individuals. Dermoscopy may be a useful non-invasive modality for evaluating skin lesions when the diagnosis of red dot basal cell carcinoma is considered. Mohs surgery is the treatment of choice; in some of the patients, the ratio of the area of the postoperative wound to that of the preoperative cancer was greater than 12:1, demonstrating a significant lateral spread of the tumor beyond the observed clinical margins of the neoplasm. In conclusion, in a patient with a personal history of actinic keratosis or nonmelanoma skin cancer, the appearance of a new red dot in a sun-exposed site should prompt additional evaluation of the skin lesion to exclude or establish the diagnosis of red dot basal cell carcinoma.

Red Dot Basal Cell Carcinoma: Report of Cases and Review of This Unique Presentation of Basal Cell Carcinoma

PubMed Central

2017-01-01

Red dot basal cell carcinoma is a unique variant of basal cell carcinoma. Including the three patients described in this report, red dot basal cell carcinoma has only been described in seven individuals. This paper describes the features of two males and one female with red dot basal cell carcinoma and reviews the characteristics of other patients with this clinical subtype of basal cell carcinoma. A 70-year-old male developed a pearly-colored papule with a red dot in the center on his nasal tip. A 71-year-old male developed a red dot surrounded by a flesh-colored papule on his left nostril. Lastly, a 74-year-old female developed a red dot within an area of erythema on her left mid back. Biopsy of the lesions all showed nodular and/or superficial basal cell carcinoma. Correlation of the clinical presentation and pathology established the diagnosis of red dot basal cell carcinoma. The tumors were treated by excision using the Mohs surgical technique. Pubmed was searched with the keyword: basal, cell, cancer, carcinoma, dot, red, and skin. The papers generated by the search and their references were reviewed. Red dot basal cell carcinoma has been described in three females and two males; the gender was not reported in two patients. The tumor was located on the nose (five patients), back (one patient) and thigh (one patient). Cancer presented as a solitary small red macule or papule; often, the carcinoma was surrounded by erythema or a flesh-colored papule. Although basal cell carcinomas usually do not blanch after a glass microscope slide is pressed against them, the red dot basal cell carcinoma blanched after diascopy in two of the patients, resulting in a delay of diagnosis in one of these individuals. Dermoscopy may be a useful non-invasive modality for evaluating skin lesions when the diagnosis of red dot basal cell carcinoma is considered. Mohs surgery is the treatment of choice; in some of the patients, the ratio of the area of the postoperative wound to that of the preoperative cancer was greater than 12:1, demonstrating a significant lateral spread of the tumor beyond the observed clinical margins of the neoplasm. In conclusion, in a patient with a personal history of actinic keratosis or nonmelanoma skin cancer, the appearance of a new red dot in a sun-exposed site should prompt additional evaluation of the skin lesion to exclude or establish the diagnosis of red dot basal cell carcinoma. PMID:28465868

Determinants of satisfaction with the health state of the facial skin in patients undergoing surgery for facial basal cell carcinoma.

PubMed

Essers, Brigitte A B; Nieman, Fred H M; Prins, Martin H; Krekels, Gertruud A M; Smeets, Nicole W J; Neumann, H A Martino

2006-02-01

The main objective of the study was to assess which health beliefs predict and explain satisfaction with the facial health state of patients undergoing surgery for basal cell carcinoma. Data were collected by administering a newly developed questionnaire pre-operatively and 6 months post-operatively (n = 222). Results show that satisfaction as measured by post-operative worrying, susceptibility and fear of developing a new BCC at other facial sites can be predicted by pre-operative health beliefs. In addition, some patients an increase in perceived susceptibility, fear of recurrence of BCC on the same site or fear of developing a new BCC at other facial sites. Our findings indicate that both pre- and post-operative perceptions predict and explain for a substantial part the extent to which patients are satisfied with their facial health state 6 months after surgery. Administering a short questionnaire at the start of the treatment period will give physicians a better understanding of how patients experience this skin disease. It will also help them to adjust information about BCC and its consequences to the needs of the patient.

Skin Cancer Can Strike Anyone

MedlinePlus

... The two most common types are basal cell cancer and squamous cell cancer. Melanoma, a more serious type of skin cancer, ... million people are treated for basal cell or squamous cell skin cancer each year. Basal cell skin cancer is several ...

A basal stem cell signature identifies aggressive prostate cancer phenotypes

PubMed Central

Smith, Bryan A.; Sokolov, Artem; Uzunangelov, Vladislav; Baertsch, Robert; Newton, Yulia; Graim, Kiley; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M.; Witte, Owen N.

2015-01-01

Evidence from numerous cancers suggests that increased aggressiveness is accompanied by up-regulation of signaling pathways and acquisition of properties common to stem cells. It is unclear if different subtypes of late-stage cancer vary in stemness properties and whether or not these subtypes are transcriptionally similar to normal tissue stem cells. We report a gene signature specific for human prostate basal cells that is differentially enriched in various phenotypes of late-stage metastatic prostate cancer. We FACS-purified and transcriptionally profiled basal and luminal epithelial populations from the benign and cancerous regions of primary human prostates. High-throughput RNA sequencing showed the basal population to be defined by genes associated with stem cell signaling programs and invasiveness. Application of a 91-gene basal signature to gene expression datasets from patients with organ-confined or hormone-refractory metastatic prostate cancer revealed that metastatic small cell neuroendocrine carcinoma was molecularly more stem-like than either metastatic adenocarcinoma or organ-confined adenocarcinoma. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common between prostate small cell neuroendocrine carcinoma and primary prostate basal cells. Taken together, our data suggest that aggressive prostate cancer shares a conserved transcriptional program with normal adult prostate basal stem cells. PMID:26460041

Predictive variables for the biological behaviour of basal cell carcinoma of the face: relevance of morphometry of the nuclei.

PubMed

Appel, T; Bierhoff, E; Appel, K; von Lindern, J-J; Bergé, S; Niederhagen, B

2003-06-01

We did a morphometric analysis of 130 histological sections of basal cell carcinoma (BCC) of the face to find out whether morphometric variables in the structure of the nuclei of BCC cells could serve as predictors of the biological behaviour. We considered the following variables: maximum and minimum diameters, perimeter, nuclear area and five form factors that characterise and quantify the shape of a structure (axis ratio, shape factor, nuclear contour index, nuclear roundness and circumference ratio). We did a statistical analysis of primary and recurring tumours and four histology-based groups (multifocal superficial BCCs, nodular BCCs, sclerosing BCCs and miscellaneous forms) using a two-sided t test for independent samples. Multifocal superficial BCCs showed significantly smaller values for the directly measured variables (maximum and minimum diameters, perimeter and nuclear area). Morphometry could not distinguish between primary and recurring tumours.

Photodynamic therapy for basal cell carcinoma.

PubMed

Fargnoli, Maria Concetta; Peris, Ketty

2015-11-01

Topical photodynamic therapy is an effective and safe noninvasive treatment for low-risk basal cell carcinoma, with the advantage of an excellent cosmetic outcome. Efficacy of photodynamic therapy in basal cell carcinoma is supported by substantial research and clinical trials. In this article, we review the procedure, indications and clinical evidences for the use of photodynamic therapy in the treatment of basal cell carcinoma.

Metastatic Basal cell carcinoma accompanying gorlin syndrome.

PubMed

Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel

2014-01-01

Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

Metastatic Basal Cell Carcinoma Accompanying Gorlin Syndrome

PubMed Central

Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel

2014-01-01

Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome. PMID:25506011

Circular RNA expression in basal cell carcinoma.

PubMed

Sand, Michael; Bechara, Falk G; Sand, Daniel; Gambichler, Thilo; Hahn, Stephan A; Bromba, Michael; Stockfleth, Eggert; Hessam, Schapoor

2016-05-01

Circular RNAs (circRNAs), are nonprotein coding RNAs consisting of a circular loop with multiple miRNA, binding sites called miRNA response elements (MREs), functioning as miRNA sponges. This study was performed to identify differentially expressed circRNAs and their MREs in basal cell carcinoma (BCC). Microarray circRNA expression profiles were acquired from BCC and control followed by qRT-PCR validation. Bioinformatical target prediction revealed multiple MREs. Sequence analysis was performed concerning MRE interaction potential with the BCC miRNome. We identified 23 upregulated and 48 downregulated circRNAs with 354 miRNA response elements capable of sequestering miRNA target sequences of the BCC miRNome. The present study describes a variety of circRNAs that are potentially involved in the molecular pathogenesis of BCC.

Lysyl oxidase-like 2 (LOXL2), a new regulator of cell polarity required for metastatic dissemination of basal-like breast carcinomas

PubMed Central

Moreno-Bueno, Gema; Salvador, Fernando; Martín, Alberto; Floristán, Alfredo; Cuevas, Eva P; Santos, Vanesa; Montes, Amalia; Morales, Saleta; Castilla, Maria Angeles; Rojo-Sebastián, Alejandro; Martínez, Alejandra; Hardisson, David; Csiszar, Katalin; Portillo, Francisco; Peinado, Héctor; Palacios, José; Cano, Amparo

2011-01-01

Basal-like breast carcinoma is characterized by the expression of basal/myoepithelial markers, undifferentiated phenotype, highly aggressive behaviour and frequent triple negative status (ESR−, PR−, Her2neu−). We have previously shown that epithelial–mesenchymal transition (EMT) occurs in basal-like breast tumours and identified Lysyl-oxidase-like 2 (LOXL2) as an EMT player and poor prognosis marker in squamous cell carcinomas. We now show that LOXL2 mRNA is overexpressed in basal-like human breast carcinomas. Breast carcinoma cell lines with basal-like phenotype show a specific cytoplasmic/perinuclear LOXL2 expression, and this subcellular distribution is significantly associated with distant metastatic incidence in basal-like breast carcinomas. LOXL2 silencing in basal-like carcinoma cells induces a mesenchymal-epithelial transition (MET) associated with a decrease of tumourigenicity and suppression of metastatic potential. Mechanistic studies indicate that LOXL2 maintains the mesenchymal phenotype of basal-like carcinoma cells by a novel mechanism involving transcriptional downregulation of Lgl2 and claudin1 and disorganization of cell polarity and tight junction complexes. Therefore, intracellular LOXL2 is a new candidate marker of basal-like carcinomas and a target to block metastatic dissemination of this aggressive breast tumour subtype. PMID:21732535

Agent-based modeling of autophagy reveals emergent regulatory behavior of spatio-temporal autophagy dynamics.

PubMed

Börlin, Christoph S; Lang, Verena; Hamacher-Brady, Anne; Brady, Nathan R

2014-09-10

Autophagy is a vesicle-mediated pathway for lysosomal degradation, essential under basal and stressed conditions. Various cellular components, including specific proteins, protein aggregates, organelles and intracellular pathogens, are targets for autophagic degradation. Thereby, autophagy controls numerous vital physiological and pathophysiological functions, including cell signaling, differentiation, turnover of cellular components and pathogen defense. Moreover, autophagy enables the cell to recycle cellular components to metabolic substrates, thereby permitting prolonged survival under low nutrient conditions. Due to the multi-faceted roles for autophagy in maintaining cellular and organismal homeostasis and responding to diverse stresses, malfunction of autophagy contributes to both chronic and acute pathologies. We applied a systems biology approach to improve the understanding of this complex cellular process of autophagy. All autophagy pathway vesicle activities, i.e. creation, movement, fusion and degradation, are highly dynamic, temporally and spatially, and under various forms of regulation. We therefore developed an agent-based model (ABM) to represent individual components of the autophagy pathway, subcellular vesicle dynamics and metabolic feedback with the cellular environment, thereby providing a framework to investigate spatio-temporal aspects of autophagy regulation and dynamic behavior. The rules defining our ABM were derived from literature and from high-resolution images of autophagy markers under basal and activated conditions. Key model parameters were fit with an iterative method using a genetic algorithm and a predefined fitness function. From this approach, we found that accurate prediction of spatio-temporal behavior required increasing model complexity by implementing functional integration of autophagy with the cellular nutrient state. The resulting model is able to reproduce short-term autophagic flux measurements (up to 3 hours) under basal and activated autophagy conditions, and to measure the degree of cell-to-cell variability. Moreover, we experimentally confirmed two model predictions, namely (i) peri-nuclear concentration of autophagosomes and (ii) inhibitory lysosomal feedback on mTOR signaling. Agent-based modeling represents a novel approach to investigate autophagy dynamics, function and dysfunction with high biological realism. Our model accurately recapitulates short-term behavior and cell-to-cell variability under basal and activated conditions of autophagy. Further, this approach also allows investigation of long-term behaviors emerging from biologically-relevant alterations to vesicle trafficking and metabolic state.

Airway Basal Cell Heterogeneity and Lung Squamous Cell Carcinoma.

PubMed

Hynds, Robert E; Janes, Sam M

2017-09-01

Basal cells are stem/progenitor cells that maintain airway homeostasis, enact repair following epithelial injury, and are a candidate cell-of-origin for lung squamous cell carcinoma. Heterogeneity of basal cells is recognized in terms of gene expression and differentiation capacity. In this Issue, Pagano and colleagues isolate a subset of immortalized basal cells that are characterized by high motility, suggesting that they might also be heterogeneous in their biophysical properties. Motility-selected cells displayed an increased ability to colonize the lung in vivo The possible implications of these findings are discussed in terms of basal cell heterogeneity, epithelial cell migration, and modeling of metastasis that occurs early in cancer evolution. Cancer Prev Res; 10(9); 491-3. ©2017 AACR See related article by Pagano et al., p. 514 . ©2017 American Association for Cancer Research.

Adenoid basal hyperplasia of the uterine cervix: a lesion of reserve cell type, distinct from adenoid basal carcinoma.

PubMed

Kerdraon, Olivier; Cornélius, Aurélie; Farine, Marie-Odile; Boulanger, Loïc; Wacrenier, Agnès

2012-12-01

Adenoid basal hyperplasia is an underrecognized cervical lesion, resembling adenoid basal carcinoma, except the absence of deep invasion into the stroma. We report a series of 10 cases, all extending less than 1 mm from the basement membrane. Our results support the hypothesis that adenoid basal hyperplasia arises from reserve cells of the cervix. Lesions were found close to the squamocolumnar junction, in continuity with the nearby subcolumnar reserve cells. They shared the same morphology and immunoprofile using a panel of 4 antibodies (keratin 5/6, keratin 14, keratin 7 and p63) designed to differentiate reserve cells from mature squamous cells and endocervical columnar cells. We detected no human papillomavirus infection by in situ hybridization targeting high-risk human papillomavirus, which was concordant with the absence of immunohistochemical p16 expression. We demonstrated human papillomavirus infection in 4 (80%) of 5 adenoid basal carcinoma, which is in the same range as previous studies (88%). Thus, adenoid basal hyperplasia should be distinguished from adenoid basal carcinoma because they imply different risk of human papillomavirus infection and of subsequent association with high-grade invasive carcinoma. In our series, the most reliable morphological parameters to differentiate adenoid basal hyperplasia from adenoid basal carcinoma were the depth of the lesion and the size of the lesion nests. Furthermore, squamous differentiation was rare in adenoid basal hyperplasia and constant in adenoid basal carcinoma. Finally, any mitotic activity and/or an increase of Ki67 labeling index should raise the hypothesis of adenoid basal carcinoma. Copyright © 2012 Elsevier Inc. All rights reserved.

Airway Basal Cells. The “Smoking Gun” of Chronic Obstructive Pulmonary Disease

PubMed Central

2014-01-01

The earliest abnormality in the lung associated with smoking is hyperplasia of airway basal cells, the stem/progenitor cells of the ciliated and secretory cells that are central to pulmonary host defense. Using cell biology and ’omics technologies to assess basal cells isolated from bronchoscopic brushings of nonsmokers, smokers, and smokers with chronic obstructive pulmonary disease (COPD), compelling evidence has been provided in support of the concept that airway basal cells are central to the pathogenesis of smoking-associated lung diseases. When confronted by the chronic stress of smoking, airway basal cells become disorderly, regress to a more primitive state, behave as dictated by their inheritance, are susceptible to acquired changes in their genome, lose the capacity to regenerate the epithelium, are responsible for the major changes in the airway that characterize COPD, and, with persistent stress, can undergo malignant transformation. Together, these observations led to the conclusion that accelerated loss of lung function in susceptible individuals begins with disordered airway basal cell biology (i.e., that airway basal cells are the “smoking gun” of COPD, a potential target for the development of therapies to prevent smoking-related lung disorders). PMID:25354273

Correlated alterations in prostate basal cell layer and basement membrane

PubMed Central

Liu, Aijun; Wei, Lixin; Gardner, William A.; Deng, Chu-Xia; Man, Yan-Gao

2009-01-01

Our recent studies revealed that focal basal cell layer disruption (FBCLD) induced auto-immunoreactions represented a contributing factor for human prostate tumor progression and invasion. As the basement membrane surrounds and attaches to the basal cell layer, our current study assessed whether FBCLD would impact the physical integrity of the associated basement membrane. Paraffin sections from 25-human prostate tumors were subjected to double immunohistochemistry to simultaneously elucidate the basal cell layer and the basement membrane with corresponding biomarkers. The physical integrity of the basement membrane overlying FBCLD was examined to determine the extent of correlated alterations. Of a total of 89 FBCLD encountered, 76 (85 %) showed correlated alterations in the overlying basement membrane, which included distinct focal disruptions or fragmentations. In the remaining 13 (15%) FBCLD, the overlying basement membrane showed significant attenuation or reduction of the immunostaining intensity. The basement membrane in all or nearly all ducts or acini with p63 positive basal cells was substantially thicker and more uniform than that in ducts or acini without p63 positive basal cells, and also, a vast majority of the focal disruptions occurred near basal cells that lack p63 expression. These findings suggest that focal disruptions in the basal cell layer and alterations in the basement membrane are correlated events and that the physical and functional status of the basal cells could significantly impact the physical integrity of the overlying basement membrane. As the degradation of both the basal cell layer and the basement membrane is a pre-requisite for prostate tumor invasion or progression, ducts or acini with focally disrupted basal cell layer and basement membrane are likely at greater risk to develop invasive lesions. Thus, further elucidation of the specific molecules and mechanism associated with these events may lead to the development of a more effective alternative for repeat biopsy to monitor tumor progression and invasion. PMID:19343113

Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).

PubMed

Bresler, Scott C; Padwa, Bonnie L; Granter, Scott R

2016-06-01

Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy.

Sequential development of apical-basal and planar polarities in aggregating epitheliomuscular cells of Hydra.

PubMed

Seybold, Anna; Salvenmoser, Willi; Hobmayer, Bert

2016-04-01

Apical-basal and planar cell polarities are hallmarks of metazoan epithelia required to separate internal and external environments and to regulate trans- and intracellular transport, cytoskeletal organization, and morphogenesis. Mechanisms of cell polarization have been intensively studied in bilaterian model organisms, particularly in early embryos and cultured cells, while cell polarity in pre-bilaterian tissues is poorly understood. Here, we have studied apical-basal and planar polarization in regenerating (aggregating) clusters of epitheliomuscular cells of Hydra, a simple representative of the ancestral, pre-bilaterian phylum Cnidaria. Immediately after dissociation, single epitheliomuscular cells do not exhibit cellular polarity, but they polarize de novo during aggregation. Reestablishment of the Hydra-specific epithelial bilayer is a result of short-range cell sorting. In the early phase of aggregation, apical-basal polarization starts with an enlargement of the epithelial apical-basal diameter and by the development of belt-like apical septate junctions. Specification of the basal pole of epithelial cells occurs shortly later and is linked to synthesis of mesoglea, development of hemidesmosome-like junctions, and formation of desmosome-like junctions connecting the basal myonemes of neighbouring cells. Planar polarization starts, while apical-basal polarization is already ongoing. It is executed gradually starting with cell-autonomous formation, parallelization, and condensation of myonemes at the basal end of each epithelial cell and continuing with a final planar alignment of epitheliomuscular cells at the tissue level. Our findings reveal that epithelial polarization in Hydra aggregates occurs in defined steps well accessible by histological and ultrastructural techniques and they will provide a basis for future molecular studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of KEAP1/NRF2 and TP53 mutations in lung squamous cell carcinoma development and radiotherapy response prediction

PubMed Central

Jeong, Youngtae; Hoang, Ngoc T.; Lovejoy, Alexander; Stehr, Henning; Newman, Aaron M.; Gentles, Andrew J.; Kong, William; Truong, Diana; Martin, Shanique; Chaudhuri, Aadel; Heiser, Diane; Zhou, Li; Say, Carmen; Carter, Justin N.; Hiniker, Susan M.; Loo, Billy W.; West, Robert B.; Beachy, Philip; Alizadeh, Ash A.; Diehn, Maximilian

2016-01-01

Lung squamous cell carcinomas (LSCC) pathogenesis remains incompletely understood and biomarkers predicting treatment response remain lacking. Here we describe novel murine LSCC models driven by loss of Trp53 and Keap1, both of which are frequently mutated in human LSCCs. Homozygous inactivation of Keap1 or Trp53 promoted airway basal stem cell (ABSC) self-renewal, suggesting that mutations in these genes lead to expansion of mutant stem cell clones. Deletion of Trp53 and Keap1 in ABSCs, but not more differentiated tracheal cells, produced tumors recapitulating histological and molecular features of human LSCCs, indicating that they represent the likely cell of origin in this model. Deletion of Keap1 promoted tumor aggressiveness, metastasis, and resistance to oxidative stress and radiotherapy (RT). KEAP1/NRF2 mutation status predicted risk of local recurrence after RT in non-small lung cancer (NSCLC) patients and could be non-invasively identified in circulating tumor DNA. Thus, KEAP1/NRF2 mutations could serve as predictive biomarkers for personalization of therapeutic strategies for NSCLCs. PMID:27663899

Nevoid Basal Cell Carcinoma Syndrome

MedlinePlus

... develops. Some individuals may have thousands of basal cell cancers in areas of skin that are exposed to ... have been approved to treat people with basal cell cancers that have spread in the body or that ...

Cooperative transformation and coexpression of bovine papillomavirus type 1 E5 and E7 proteins.

PubMed

Bohl, J; Hull, B; Vande Pol, S B

2001-01-01

Productively infected bovine fibropapillomas were examined for bovine papillomavirus type 1 (BPV-1) E7 localization. BPV-1 E7 was observed in the cytoplasm of basal and lower spinous epithelial cells, coexpressed in the cytoplasm of basal cells with the E5 oncoprotein. E7 was also observed in nucleoli throughout the basal and spinous layers but not in the granular cell layer. Ectopic expression of E7 in cultured epithelial cells gave rise to localization similar to that seen in productive fibropapillomas, with cytoplasmic and nucleolar expression observed. Consistent with the coexpression of E7 and E5 in basal keratinocytes, BPV-1 E7 cooperated with E5 as well as E6 in an anchorage independence transformation assay. While E5 is expressed in both basal and superficial differentiating keratinocytes, BPV-1 E7 is only observed in basal and lower spinous epithelial cells. Therefore, BPV-1 E7 may serve to modulate the cellular response of basal epithelial cells to E5 expression.

Isolation and Characterization of Prostate Cancer Stem Cells

DTIC Science & Technology

2009-08-01

The Prostate Manuscript ID: PROS-09-224.R1 Wiley - Manuscript type: Original Article Date Submitted by the Author: 18-Sep-2009 Complete List of ...subpopulation of basal cells has stem cell characteristics raises some interesting questions about the cell of origin for prostate cancer. Can both basal...positively for AMACR and the retention of 7 a p63+ basal layer, the basal-derived lesions fulfill the histologic criteria used

Basal cell carcinoma of the nipple - an unusual location in a male patient.

PubMed

Avci, Oktay; Pabuççuoğlu, Uğur; Koçdor, M Ali; Unlü, Mehtat; Akin, Ciler; Soyal, Cüneyt; Canda, Tülay

2008-02-01

Although basal cell carcinoma is extremely common, it only rarely occurs on the nipple. Men are affected more often than women. Basal cell carcinoma of the nipple-areola complex may be more aggressive as metastases to regional lymph nodes have been reported. We report a basal cell carcinoma of the nipple with features of a fibroepithelioma of Pinkus in a man and review the literature.

Pigmented basal cell carcinoma mimicking a superficial spreading melanoma.

PubMed

Hasbún Acuña, Paula; Cullen Aravena, Roberto; Maturana Donaire, César; Ares Mora, Raúl; Porras Kusmanic, Ninoska

2016-12-20

Basal cell carcinoma is the most common form of skin cancer, especially in elderly people. Pigmented basal cell carcinoma is a rare subtype and has been described in the literature as a nodular and hyperpigmented lesion; rarely, it can appear as an extensive pigmented plate, which may be clinically indistinguishable from superficial spreading melanoma and Bowen disease. Dermatoscopy has a high sensitivity in the diagnosis of basal cell carcinoma. When Menzies criteria are used; however, the final diagnosis is made by histopathology. The objective of the present report is to analyze the case of a patient with pigmented basal cell carcinoma simulating a superficial spreading melanoma.

Giant morphea-form basal cell carcinoma of the umbilicus: Successful debulking with vismodegib.

PubMed

Orduz Robledo, Mariana; Lebas, Eve; Reginster, Marie-Annick; Baghaie, Mahmoud; Groves, Sabine; Nikkels, Arjen F

2018-01-01

Basal cell carcinoma of the umbilicus is very rare. The nodular subtype is the main representative. Giant basal cell carcinomas represent around 1% of all basal cell carcinomas. The hedgehog pathway inhibitor vismodegib is indicated for advanced basal cell carcinoma and CD56-negative immunostaining seems indicative for successful treatment. A 54-year-old man presented a 10 cm × 14 cm large and 4.5 cm deep morphea-form basal cell carcinoma with faint immunohistochemical CD56 expression arising from the umbilicus. A sequential treatment was initiated with debulking using vismodegib 150 mg per day for 4 months, followed by reconstructive surgery. To the best of our knowledge, this is the first report of a giant basal cell carcinoma of the morphea-form type of the umbilicus. The sequential treatment plan reduces the duration of vismodegib inherent adverse effects and significantly reduces the tumor mass prior to surgery. Besides increasing adherence to vismodegib treatment, this approach facilitates the surgical technique and improves cosmetic outcome.

Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer

PubMed Central

Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R.; Tang, Dean G.

2016-01-01

The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. PMID:26924072

Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer.

PubMed

Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R; Tang, Dean G

2016-02-29

The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

Is basal ultrasensitive measurement of calcitonin capable of substituting for the pentagastrin-stimulation test?

PubMed

Pina, Géraldine; Dubois, Séverine; Murat, Arnaud; Berger, Nicole; Niccoli, Patricia; Peix, Jean-Louis; Cohen, Régis; Guillausseau, Claudine; Charrie, Anne; Chabre, Olivier; Cornu, Catherine; Borson-Chazot, Françoise; Rohmer, Vincent

2013-03-01

To evaluate a second-generation assay for basal serum calcitonin (CT) measurements compared with the pentagastrin-stimulation test for the diagnosis of inherited medullary thyroid carcinoma (MTC) and the follow-up of patients with MTC after surgery. Recent American Thyroid Association recommendations suggest the use of basal CT alone to diagnose and assess follow-up of MTC as the pentagastrin (Pg) test is unavailable in many countries. Multicentric prospective study. A total of 162 patients with basal CT <10 ng/l were included: 54 asymptomatic patients harboured noncysteine 'rearranged during transfection' (RET) proto-oncogene mutations and 108 patients had entered follow-up of MTC after surgery. All patients underwent basal and Pg-stimulated CT measurements using a second-generation assay with 5-ng/l functional sensitivity. Ninety-five per cent of patients with basal CT ≥ 5 ng/l and 25% of patients with basal CT <5 ng/l had a positive Pg-stimulation test (Pg CT >10 ng/l). Compared with the reference Pg test, basal CT ≥ 5 ng/l had 99% specificity, a 95%-positive predictive value but only 35% sensitivity (P < 0.0001). Overall, there were 31% less false-negative results using a 5-ng/l threshold for basal CT instead of the previously used 10-ng/l threshold. The ultrasensitive CT assay reduces the false-negative rate of basal CT measurements when diagnosing familial MTC and in postoperative follow-up compared with previously used assays. However, its sensitivity to detect C-cell disease remains lower than that of the Pg-stimulation test. © 2012 Blackwell Publishing Ltd.

Basal cell carcinoma arising in association with a maxillary keratocyst in a patient with Gorlin-Goltz syndrome. Report of a case.

PubMed

Lazaridou, Maria Nikolaou; Dimitrakopoulos, Ioannis; Tilaveridis, Ioannis; Iliopoulos, Christos; Heva, Antigoni

2012-03-01

Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome, is an autosomal dominant inherited disorder which is characterized by the presence of multiple basal cell carcinomas, maxillary keratocysts, and musculoskeletal anomalies. We present a case of a patient suffering from Gorlin-Goltz syndrome who developed an intraosseous basal cell carcinoma associated with a recurrent maxillary keratocyst. To our knowledge, this is the first case of malignant transformation of a keratocyst into a basal cell carcinoma described in the literature. This case highlights the importance of careful histologic examination of keratocysts excised in patients suffering from Gorlin-Goltz syndrome.

Striated Acto-Myosin Fibers Can Reorganize and Register in Response to Elastic Interactions with the Matrix

PubMed Central

Friedrich, Benjamin M.; Buxboim, Amnon; Discher, Dennis E.; Safran, Samuel A.

2011-01-01

The remarkable striation of muscle has fascinated many for centuries. In developing muscle cells, as well as in many adherent, nonmuscle cell types, striated, stress fiberlike structures with sarcomere-periodicity tend to register: Based on several studies, neighboring, parallel fibers at the basal membrane of cultured cells establish registry of their respective periodic sarcomeric architecture, but, to our knowledge, the mechanism has not yet been identified. Here, we propose for cells plated on an elastic substrate or adhered to a neighboring cell, that acto-myosin contractility in striated fibers close to the basal membrane induces substrate strain that gives rise to an elastic interaction between neighboring striated fibers, which in turn favors interfiber registry. Our physical theory predicts a dependence of interfiber registry on externally controllable elastic properties of the substrate. In developing muscle cells, registry of striated fibers (premyofibrils and nascent myofibrils) has been suggested as one major pathway of myofibrillogenesis, where it precedes the fusion of neighboring fibers. This suggests a mechanical basis for the optimal myofibrillogenesis on muscle-mimetic elastic substrates that was recently observed by several groups in cultures of mouse-, human-, and chick-derived muscle cells. PMID:21641316

BMP-driven NRF2 activation in esophageal basal cell differentiation and eosinophilic esophagitis

PubMed Central

Jiang, Ming; Ku, Wei-Yao; Zhou, Zhongren; Dellon, Evan S.; Falk, Gary W.; Nakagawa, Hiroshi; Wang, Mei-Lun; Liu, Kuancan; Wang, Jun; Katzka, David A.; Peters, Jeffrey H.; Lan, Xiaopeng; Que, Jianwen

2015-01-01

Tissue homeostasis requires balanced self-renewal and differentiation of stem/progenitor cells, especially in tissues that are constantly replenished like the esophagus. Disruption of this balance is associated with pathological conditions, including eosinophilic esophagitis (EoE), in which basal progenitor cells become hyperplastic upon proinflammatory stimulation. However, how basal cells respond to the inflammatory environment at the molecular level remains undetermined. We previously reported that the bone morphogenetic protein (BMP) signaling pathway is critical for epithelial morphogenesis in the embryonic esophagus. Here, we address how this pathway regulates tissue homeostasis and EoE development in the adult esophagus. BMP signaling was specifically activated in differentiated squamous epithelium, but not in basal progenitor cells, which express the BMP antagonist follistatin. Previous reports indicate that increased BMP activity promotes Barrett’s intestinal differentiation; however, in mice, basal progenitor cell–specific expression of constitutively active BMP promoted squamous differentiation. Moreover, BMP activation increased intracellular ROS levels, initiating an NRF2-mediated oxidative response during basal progenitor cell differentiation. In both a mouse EoE model and human biopsies, reduced squamous differentiation was associated with high levels of follistatin and disrupted BMP/NRF2 pathways. We therefore propose a model in which normal squamous differentiation of basal progenitor cells is mediated by BMP-driven NRF2 activation and basal cell hyperplasia is promoted by disruption of BMP signaling in EoE. PMID:25774506

Tazarotene-induced gene 3 is suppressed in basal cell carcinomas and reversed in vivo by tazarotene application.

PubMed

Duvic, Madeleine; Ni, Xiao; Talpur, Rakhashandra; Herne, Kelly; Schulz, Claudia; Sui, Dawen; Ward, Staci; Joseph, Aaron; Hazarika, Parul

2003-10-01

Basal cell carcinomas are the most common form of skin cancer. Tazarotene is a retinoic acid receptor selective retinoid that upregulates a tumor suppressor, tazarotene-induced gene 3 (TIG-3), in keratinocytes and psoriasis. Expression of TIG-3 in basal cell carcinomas was studied in an opened-label pilot biomarker study of 22 patients with basal cell carcinomas who applied tazarotene 0.1% gel for up to 12 wk prior to excision. Nineteen paired baseline and treated specimens were compared using immunohistochemistry and in situ hybridization. Compared to overlying normal epidermis, TIG-3 protein and mRNA were decreased in 14 and 18 of 19 basal cell carcinomas (74% and 95%), respectively (p < 0.001). Tazarotene treatment was associated with increased TIG-3 protein and mRNA expression in basal cell carcinomas compared to baseline levels (p < or = 0.001 and p = 0.028, respectively). Sixty percent of basal cell carcinomas treated with tazarotene decreased in size by at least 25%. Ten of 19 lesions improved histologically, including three complete responses. There was a correlation between the increased expression of TIG-3 protein and histologic improvement (p = 0.020), suggesting that suppression of TIG-3 may underlie the development of basal cell carcinomas. This association suggests that reversal of TIG-3 expression may help to explain the mechanism of retinoid action in epidermal differentiation and chemoprevention.

Protein profile of basal prostate epithelial progenitor cells--stage-specific embryonal antigen 4 expressing cells have enhanced regenerative potential in vivo.

PubMed

Höfner, Thomas; Klein, Corinna; Eisen, Christian; Rigo-Watermeier, Teresa; Haferkamp, Axel; Sprick, Martin R

2016-04-01

The long-term propagation of basal prostate progenitor cells ex vivo has been very difficult in the past. The development of novel methods to expand prostate progenitor cells in vitro allows determining their cell surface phenotype in greater detail. Mouse (Lin(-)Sca-1(+) CD49f(+) Trop2(high)-phenotype) and human (Lin(-) CD49f(+) TROP2(high)) basal prostate progenitor cells were expanded in vitro. Human and mouse cells were screened using 242 anti-human or 176 antimouse monoclonal antibodies recognizing the cell surface protein profile. Quantitative expression was evaluated at the single-cell level using flow cytometry. Differentially expressed cell surface proteins were evaluated in conjunction with the known CD49f(+)/TROP2(high) phenotype of basal prostate progenitor cells and characterized by in vivo sandwich-transplantation experiments using nude mice. The phenotype of basal prostate progenitor cells was determined as CD9(+)/CD24(+)/CD29(+)/CD44(+)/CD47(+)/CD49f(+)/CD104(+)/CD147(+)/CD326(+)/Trop2(high) of mouse as well as human origin. Our analysis revealed several proteins, such as CD13, Syndecan-1 and stage-specific embryonal antigens (SSEAs), as being differentially expressed on murine and human CD49f(+) TROP2(+) basal prostate progenitor cells. Transplantation experiments suggest that CD49f(+) TROP2(high) SSEA-4(high) human prostate basal progenitor cells to be more potent to regenerate prostate tubules in vivo as compared with CD49f(+) TROP2(high) or CD49f(+) TROP2(high) SSEA-4(low) cells. Determination of the cell surface protein profile of functionally defined murine and human basal prostate progenitor cells reveals differentially expressed proteins that may change the potency and regenerative function of epithelial progenitor cells within the prostate. SSEA-4 is a candidate cell surface marker that putatively enables a more accurate identification of the basal PESC lineage. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Characterization of C-type natriuretic peptide receptors in human mesangial cells.

PubMed

Zhao, J; Ardaillou, N; Lu, C Y; Placier, S; Pham, P; Badre, L; Cambar, J; Ardaillou, R

1994-09-01

Our aim was to examine whether the human glomerulus was a target for C-type natriuretic peptide (CNP) and how A, B and C receptors of natriuretic peptides (ANPR-A, ANPR-B, ANPR-C) were distributed in glomerular mesangial and epithelial cells. CNP stimulated cyclic GMP production in cultured human mesangial and epithelial cells with similar threshold concentrations (1 nM) and maximum effects (basal value x 30 at 1 microM). In contrast, atrial natriuretic peptide (ANP) was only stimulatory in epithelial cells. [125I] CNP bound specifically to mesangial cells with a Kd of 0.47 nM and Bmax of 42 fmol/mg. Equilibrium of binding was obtained after four to five hours at +4 degrees C and nonspecific binding represented 10 to 20% of total binding. HS142-1 (100 micrograms/ml), a specific inhibitor of ANPR-A and ANPR-B, suppressed 90% of CNP-dependent cyclic GMP production whereas it had little effect on [125I]-CNP binding, suggesting that C receptors were largely predominant in mesangial cells. No biological effect of CNP on mesangial cells, including change in basal or angiotensin II-induced contractility and inhibition of basal or serum-dependent proliferation, could be demonstrated. Similar results were obtained with 8-bromo-cyclic GMP and sodium nitroprusside. Intraglomerular localization of ANPR-A, ANPR-B and ANPR-C mRNA was studied using reverse transcriptase-polymerase chain reaction with amplification of their corresponding cDNA by different primers. Amplification products were identified on gel electrophoresis by their predicted sizes and sequencing. ANPR-A, ANPR-B and ANPR-C mRNA were present in epithelial cells whereas only ANPR-B and ANPR-C mRNA were detected in mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

O6-methylguanine-DNA methyltransferase as a prognostic and predictive marker for basal-like breast cancer treated with cyclophosphamide-based chemotherapy

PubMed Central

ISONO, SAYURI; FUJISHIMA, MAKOTO; AZUMI, TATSUYA; HASHIMOTO, YUKIHIKO; KOMOIKE, YOSHIFUMI; YUKAWA, MASAO; WATATANI, MASAHIRO

2014-01-01

The O6-methylguanine-DNA methyltransferase (MGMT) protein protects cells from alkylating agents by removing alkyl groups from the O6-position of guanine. However, its effect on DNA damage induced by cyclophosphamide (CPM) is unclear. The present study investigated whether MGMT expression was correlated with prognosis in patients with breast cancer that was managed according to a common therapeutic protocol or treated with CPM-based chemotherapy. The intrinsic subtypes and MGMT protein expression levels were assessed in 635 consecutive patients with breast cancer using immunohistochemistry. In total, 425 (67%) luminal A, 95 (15%) luminal B, 47 (7%) human epidermal growth factor receptor-2+/estrogen receptor− (HER2+/ER−) and 48 (8%) basal-like subtypes were identified. Of these, MGMT positivity was identified in 398 (63%) of 635 breast cancers; 68% of luminal A, 67% of luminal B, 30% of HER2+/ER− and 46% of basal-like subtypes were positive. The overall survival (OS) and disease-free survival (DFS) rates did not significantly differ according to the MGMT status among patients with luminal A, luminal B or HER2+/ER− subtypes, and patients with MGMT-negative basal-like cancers tended to have a longer DFS, but not a significantly longer OS time. CPM-containing chemotherapy was administered to 26%, 40%, 47% and 31% of patients with luminal A, luminal B, HER2+/ER− and basal-like tumors, respectively. Although the MGMT status and clinical outcomes of patients with the luminal A, luminal B or HER2+/ER− subtypes treated with CPM were not significantly correlated, the patients with MGMT-negative basal-like tumors who received CPM exhibited significantly improved DFS and OS compared with the CPM-treated patients with MGMT-positive tumors. MGMT may be a useful prognostic and predictive marker for CPM-containing chemotherapy in basal-like breast cancer. PMID:24932232

O6-methylguanine-DNA methyltransferase as a prognostic and predictive marker for basal-like breast cancer treated with cyclophosphamide-based chemotherapy.

PubMed

Isono, Sayuri; Fujishima, Makoto; Azumi, Tatsuya; Hashimoto, Yukihiko; Komoike, Yoshifumi; Yukawa, Masao; Watatani, Masahiro

2014-06-01

The O 6 -methylguanine-DNA methyltransferase (MGMT) protein protects cells from alkylating agents by removing alkyl groups from the O 6 -position of guanine. However, its effect on DNA damage induced by cyclophosphamide (CPM) is unclear. The present study investigated whether MGMT expression was correlated with prognosis in patients with breast cancer that was managed according to a common therapeutic protocol or treated with CPM-based chemotherapy. The intrinsic subtypes and MGMT protein expression levels were assessed in 635 consecutive patients with breast cancer using immunohistochemistry. In total, 425 (67%) luminal A, 95 (15%) luminal B, 47 (7%) human epidermal growth factor receptor-2 + /estrogen receptor - (HER2 + /ER - ) and 48 (8%) basal-like subtypes were identified. Of these, MGMT positivity was identified in 398 (63%) of 635 breast cancers; 68% of luminal A, 67% of luminal B, 30% of HER2 + /ER - and 46% of basal-like subtypes were positive. The overall survival (OS) and disease-free survival (DFS) rates did not significantly differ according to the MGMT status among patients with luminal A, luminal B or HER2 + /ER - subtypes, and patients with MGMT-negative basal-like cancers tended to have a longer DFS, but not a significantly longer OS time. CPM-containing chemotherapy was administered to 26%, 40%, 47% and 31% of patients with luminal A, luminal B, HER2 + /ER - and basal-like tumors, respectively. Although the MGMT status and clinical outcomes of patients with the luminal A, luminal B or HER2 + /ER - subtypes treated with CPM were not significantly correlated, the patients with MGMT-negative basal-like tumors who received CPM exhibited significantly improved DFS and OS compared with the CPM-treated patients with MGMT-positive tumors. MGMT may be a useful prognostic and predictive marker for CPM-containing chemotherapy in basal-like breast cancer.

Differences in MYB expression and gene abnormalities further confirm that salivary cribriform basal cell tumors and adenoid cystic carcinoma are two distinct tumor entities.

PubMed

Tian, Zhen; Li, Lei; Zhang, Chun-Ye; Gu, Ting; Li, Jiang

2016-10-01

In practices, some cases of salivary basal cell tumors that consist mainly of cribriform growth pattern are difficult to differentiate from adenoid cystic carcinoma (AdCC). Identification of reliable molecular biomarkers for the differential diagnosis between them is required. Twenty-two cases of cribriform salivary basal cell tumors (at least 10% cribriform pattern present in each tumor) comprising 18 cases of basal cell adenoma (BCA) and four cases of basal cell adenocarcinoma (BcAC) were collected between 1985 and 2008. Twenty cases of cribriform AdCC were retrieved from our archives. MYB protein expression and gene abnormalities were detected in all cases by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) analyses, respectively. Neither MYB protein nor split genes were detected in any of the cases of cribriform basal cell tumors, while 55% (11/20) of cases of cribriform AdCC had MYB protein expression. High MYB expression was detected in 81.8% (9/11) cases, while low expression was found in the remaining cases. FISH analysis indicated that nine AdCC tumors with high MYB protein expression were split gene-positive, while MYB gene splitting was not detected in the 11 cases with low or absent MYB protein expression. The molecular changes in AdCC differ from those associated with cribriform basal cell tumors, which further confirms that cribriform basal cell tumors and AdCC are two distinct tumor entities. Simultaneous detection of MYB protein expression and the associated molecular changes could be beneficial in differentiating salivary cribriform basal cell tumors from AdCC. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Gene Expression and Proteome Analysis as Sources of Biomarkers in Basal Cell Carcinoma

PubMed Central

Ghita, Mihaela Adriana; Voiculescu, Suzana; Rosca, Adrian E.; Moraru, Liliana; Greabu, Maria

2016-01-01

Basal cell carcinoma (BCC) is the world's leading skin cancer in terms of frequency at the moment and its incidence continues to rise each year, leading to profound negative psychosocial and economic consequences. UV exposure is the most important environmental factor in the development of BCC in genetically predisposed individuals, this being reflected by the anatomical distribution of lesions mainly on sun-exposed skin areas. Early diagnosis and prompt management are of crucial importance in order to prevent local tissue destruction and subsequent disfigurement. Although various noninvasive or minimal invasive techniques have demonstrated their utility in increasing diagnostic accuracy of BCC and progress has been made in its treatment options, recurrent, aggressive, and metastatic variants of BCC still pose significant challenge for the healthcare system. Analysis of gene expression and proteomic profiling of tumor cells and of tumoral microenvironment in various tissues strongly suggests that certain molecules involved in skin cancer pathogenic pathways might represent novel predictive and prognostic biomarkers in BCC. PMID:27578920

Basal Cell Carcinoma with Myoepithelial Differentiation: Case Report and Literature Review.

PubMed

Cohen, Philip R

2018-01-17

Basal cell carcinoma is the most common skin cancer. Myoepithelial cells are specialized epithelial cells. Basal cell carcinoma with myoepithelial differentiation is a rare tumor. A 71-year-old man with a basal cell carcinoma with myoepithelial differentiation that presented as an asymptomatic red papule of two months duration on his forehead is described. Including the reported patient, this variant of basal cell carcinoma has been described in 16 patients: 11 men and five women. The patients ranged in age at diagnosis from 43 years to 83 years; the median age at diagnosis was 66 years. All of the tumors were located on the face-most were papules or nodules of less than 10 x 10 mm. Their pathology demonstrated two components: one was that of a typical basal cell carcinoma and the other was myoepithelioma-like in which the tumor cells were plasmacytoid or signet ring in appearance and contained abundant eosinophilic cytoplasm or hyaline inclusions or both. The myoepithelial tumor cells had variable immunohistochemical expression that included not only cytokeratin but also actin, glial fibrillary acid protein, S100, and vimentin. The most common clinical impression, prior to biopsy, was a basal cell carcinoma. The pathologic differential diagnosis included cutaneous mixed sweat gland tumor of the skin, myoepithelioma, myoepithelial carcinoma, and tumors that contain a prominent signet ring cell component (such as metastatic gastrointestinal and breast carcinoma, melanoma, plasmacytoid squamous cell carcinoma, and T-cell lymphoma). Mohs micrographic surgical excision, with complete removal of the tumor, was recommended for treatment of the carcinoma.

Basal Cell Carcinoma with Myoepithelial Differentiation: Case Report and Literature Review

PubMed Central

2018-01-01

Basal cell carcinoma is the most common skin cancer. Myoepithelial cells are specialized epithelial cells. Basal cell carcinoma with myoepithelial differentiation is a rare tumor. A 71-year-old man with a basal cell carcinoma with myoepithelial differentiation that presented as an asymptomatic red papule of two months duration on his forehead is described. Including the reported patient, this variant of basal cell carcinoma has been described in 16 patients: 11 men and five women. The patients ranged in age at diagnosis from 43 years to 83 years; the median age at diagnosis was 66 years. All of the tumors were located on the face—most were papules or nodules of less than 10 x 10 mm. Their pathology demonstrated two components: one was that of a typical basal cell carcinoma and the other was myoepithelioma-like in which the tumor cells were plasmacytoid or signet ring in appearance and contained abundant eosinophilic cytoplasm or hyaline inclusions or both. The myoepithelial tumor cells had variable immunohistochemical expression that included not only cytokeratin but also actin, glial fibrillary acid protein, S100, and vimentin. The most common clinical impression, prior to biopsy, was a basal cell carcinoma. The pathologic differential diagnosis included cutaneous mixed sweat gland tumor of the skin, myoepithelioma, myoepithelial carcinoma, and tumors that contain a prominent signet ring cell component (such as metastatic gastrointestinal and breast carcinoma, melanoma, plasmacytoid squamous cell carcinoma, and T-cell lymphoma). Mohs micrographic surgical excision, with complete removal of the tumor, was recommended for treatment of the carcinoma. PMID:29560294

Expression of heparanase in basal cell carcinoma and squamous cell carcinoma.

PubMed

Pinhal, Maria Aparecida Silva; Almeida, Maria Carolina Leal; Costa, Alessandra Scorse; Theodoro, Thérèse Rachell; Serrano, Rodrigo Lorenzetti; Machado, Carlos D'Apparecida Santos

2016-01-01

Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control). Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). The A431 strain showed significant increase in the sulfated glycosaminoglycans, increased heparanase expression and decreased hyaluronic acid, comparing to the HaCaT lineage. The mRNA expression of heparanase was significantly higher in Basal cell carcinoma and squamous cell carcinoma compared with control skin samples. It was also observed increased heparanase expression in squamous cell carcinoma compared to the Basal cell carcinoma. The glycosaminoglycans profile, as well as heparanase expression are different between HaCaT and A431 cell lines. The increased expression of heparanase in Basal cell carcinoma and squamous cell carcinoma suggests that this enzyme could be a marker for the diagnosis of such types of non-melanoma cancers, and may be useful as a target molecule for future alternative treatment.

Indoor tanning and the MC1R genotype: risk prediction for basal cell carcinoma risk in young people.

PubMed

Molinaro, Annette M; Ferrucci, Leah M; Cartmel, Brenda; Loftfield, Erikka; Leffell, David J; Bale, Allen E; Mayne, Susan T

2015-06-01

Basal cell carcinoma (BCC) incidence is increasing, particularly in young people, and can be associated with significant morbidity and treatment costs. To identify young individuals at risk of BCC, we assessed existing melanoma or overall skin cancer risk prediction models and built a novel risk prediction model, with a focus on indoor tanning and the melanocortin 1 receptor gene, MC1R. We evaluated logistic regression models among 759 non-Hispanic whites from a case-control study of patients seen between 2006 and 2010 in New Haven, Connecticut. In our data, the adjusted area under the receiver operating characteristic curve (AUC) for a model by Han et al. (Int J Cancer. 2006;119(8):1976-1984) with 7 MC1R variants was 0.72 (95% confidence interval (CI): 0.66, 0.78), while that by Smith et al. (J Clin Oncol. 2012;30(15 suppl):8574) with MC1R and indoor tanning had an AUC of 0.69 (95% CI: 0.63, 0.75). Our base model had greater predictive ability than existing models and was significantly improved when we added ever-indoor tanning, burns from indoor tanning, and MC1R (AUC = 0.77, 95% CI: 0.74, 0.81). Our early-onset BCC risk prediction model incorporating MC1R and indoor tanning extends the work of other skin cancer risk prediction models, emphasizes the value of both genotype and indoor tanning in skin cancer risk prediction in young people, and should be validated with an independent cohort. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Transient elevation of cytoplasmic calcium ion concentration at a single cell level precedes morphological changes of epidermal keratinocytes during cornification.

PubMed

Murata, Teruasa; Honda, Tetsuya; Egawa, Gyohei; Yamamoto, Yasuo; Ichijo, Ryo; Toyoshima, Fumiko; Dainichi, Teruki; Kabashima, Kenji

2018-04-26

Epidermal keratinocytes achieve sequential differentiation from basal to granular layers, and undergo a specific programmed cell death, cornification, to form an indispensable barrier of the body. Although elevation of the cytoplasmic calcium ion concentration ([Ca 2+ ] i ) is one of the factors predicted to regulate cornification, the dynamics of [Ca 2+ ] i in epidermal keratinocytes is largely unknown. Here using intravital imaging, we captured the dynamics of [Ca 2+ ] i in mouse skin. [Ca 2+ ] i was elevated in basal cells on the second time scale in three spatiotemporally distinct patterns. The transient elevation of [Ca 2+ ] i also occurred at the most apical granular layer at a single cell level, and lasted for approximately 40 min. The transient elevation of [Ca 2+ ] i at the granular layer was followed by cornification, which was completed within 10 min. This study demonstrates the tightly regulated elevation of [Ca 2+ ] i preceding the cornification of epidermal keratinocytes, providing possible clues to the mechanisms of cornification.

Essential basal cytonemes take up Hedgehog in the Drosophila wing imaginal disc.

PubMed

Chen, Weitao; Huang, Hai; Hatori, Ryo; Kornberg, Thomas B

2017-09-01

Morphogen concentration gradients that extend across developmental fields form by dispersion from source cells. In the Drosophila wing disc, Hedgehog (Hh) produced by posterior compartment cells distributes in a concentration gradient to adjacent cells of the anterior compartment. We monitored Hh:GFP after pulsed expression, and analyzed the movement and colocalization of Hh, Patched (Ptc) and Smoothened (Smo) proteins tagged with GFP or mCherry and expressed at physiological levels from bacterial artificial chromosome transgenes. Hh:GFP moved to basal subcellular locations prior to release from posterior compartment cells that express it, and was taken up by basal cytonemes that extend to the source cells. Hh and Ptc were present in puncta that moved along the basal cytonemes and formed characteristic apical-basal distributions in the anterior compartment cells. The basal cytonemes required diaphanous , SCAR , N euroglian and S ynaptobrevin , and both the Hh gradient and Hh signaling declined under conditions in which the cytonemes were compromised. These findings show that in the wing disc, Hh distributions and signaling are dependent upon basal release and uptake, and on cytoneme-mediated movement. No evidence for apical dispersion was obtained. © 2017. Published by The Company of Biologists Ltd.

Parity induces differentiation and reduces Wnt/Notch signaling ratio and proliferation potential of basal stem/progenitor cells isolated from mouse mammary epithelium

PubMed Central

2013-01-01

Introduction Early pregnancy has a strong protective effect against breast cancer in humans and rodents, but the underlying mechanism is unknown. Because breast cancers are thought to arise from specific cell subpopulations of mammary epithelia, we studied the effect of parity on the transcriptome and the differentiation/proliferation potential of specific luminal and basal mammary cells in mice. Methods Mammary epithelial cell subpopulations (luminal Sca1-, luminal Sca1+, basal stem/progenitor, and basal myoepithelial cells) were isolated by flow cytometry from parous and age-matched virgin mice and examined by using a combination of unbiased genomics, bioinformatics, in vitro colony formation, and in vivo limiting dilution transplantation assays. Specific findings were further investigated with immunohistochemistry in entire glands of parous and age-matched virgin mice. Results Transcriptome analysis revealed an upregulation of differentiation genes and a marked decrease in the Wnt/Notch signaling ratio in basal stem/progenitor cells of parous mice. Separate bioinformatics analyses showed reduced activity for the canonical Wnt transcription factor LEF1/TCF7 and increased activity for the Wnt repressor TCF3. This finding was specific for basal stem/progenitor cells and was associated with downregulation of potentially carcinogenic pathways and a reduction in the proliferation potential of this cell subpopulation in vitro and in vivo. As a possible mechanism for decreased Wnt signaling in basal stem/progenitor cells, we found a more than threefold reduction in the expression of the secreted Wnt ligand Wnt4 in total mammary cells from parous mice, which corresponded to a similar decrease in the proportion of Wnt4-secreting and estrogen/progesterone receptor-positive cells. Because recombinant Wnt4 rescued the proliferation defect of basal stem/progenitor cells in vitro, reduced Wnt4 secretion appears to be causally related to parity-induced alterations of basal stem/progenitor cell properties in mice. Conclusions By revealing that parity induces differentiation and downregulates the Wnt/Notch signaling ratio and the in vitro and in vivo proliferation potential of basal stem/progenitor cells in mice, our study sheds light on the long-term consequences of an early pregnancy. Furthermore, it opens the door to future studies assessing whether inhibitors of the Wnt pathway may be used to mimic the parity-induced protective effect against breast cancer. PMID:23621987

Differentiation Generates Paracrine Cell Pairs That Maintain Basaloid Mouse Mammary Tumors: Proof of Concept

PubMed Central

Kim, Soyoung; Goel, Shruti; Alexander, Caroline M.

2011-01-01

There is a paradox offered up by the cancer stem cell hypothesis. How are the mixed populations that are characteristic of heterogeneous solid tumors maintained at constant proportion, given their high, and different, mitotic indices? In this study, we evaluate a well-characterized mouse model of human basaloid tumors (induced by the oncogene Wnt1), which comprise mixed populations of mammary epithelial cells resembling their normal basal and luminal counterparts. We show that these cell types are substantially inter-dependent, since the MMTV LTR drives expression of Wnt1 ligand in luminal cells, whereas the functional Wnt1-responsive receptor (Lrp5) is expressed by basal cells, and both molecules are necessary for tumor growth. There is a robust tumor initiating activity (tumor stem cell) in the basal cell population, which is associated with the ability to differentiate into luminal and basal cells, to regenerate the oncogenic paracrine signaling cell pair. However, we found an additional tumor stem cell activity in the luminal cell population. Knowing that tumors depend upon Wnt1-Lrp5, we hypothesized that this stem cell must express Lrp5, and found that indeed, all the stem cell activity could be retrieved from the Lrp5-positive cell population. Interestingly, this reflects post-transcriptional acquisition of Lrp5 protein expression in luminal cells. Furthermore, this plasticity of molecular expression is reflected in plasticity of cell fate determination. Thus, in vitro, Wnt1-expressing luminal cells retro-differentiate to basal cell types, and in vivo, tumors initiated with pure luminal cells reconstitute a robust basal cell subpopulation that is indistinguishable from the populations initiated by pure basal cells. We propose this is an important proof of concept, demonstrating that bipotential tumor stem cells are essential in tumors where oncogenic ligand-receptor pairs are separated into different cell types, and suggesting that Wnt-induced molecular and fate plasticity can close paracrine loops that are usually separated into distinct cell types. PMID:21541292

Basal Cell Carcinoma

PubMed Central

Lanoue, Julien

2016-01-01

Basal cell carcinoma is the most commonly occurring cancer in the world and overall incidence is still on the rise. While typically a slow-growing tumor for which metastases is rare, basal cell carcinoma can be locally destructive and disfiguring. Given the vast prevalence of this disease, there is a significant overall burden on patient well-being and quality of life. The current mainstay of basal cell carcinoma treatment involves surgical modalities, such as electrodessication and curettage, excision, cryosurgery, and Mohs micrographic surgery. Such methods are typically reserved for localized basal cell carcinoma and offer high five-year cure rates, but come with the risk of functional impairment, disfigurement, and scarring. Here, the authors review the evidence and indications for nonsurgical treatment modalities in cases where surgery is impractical, contraindicated, or simply not desired by the patient. PMID:27386043

Vismodegib hedgehog-signaling inhibition and treatment of basal cell carcinomas as well as keratocystic odontogenic tumors in Gorlin syndrome.

PubMed

Booms, Patrick; Harth, Marc; Sader, Robert; Ghanaati, Shahram

2015-01-01

Vismodegib hedgehog signaling inhibition treatment has potential for reducing the burden of multiple skin basal cell carcinomas and jaw keratocystic odontogenic tumors. They are major criteria for the diagnosis of Gorlin syndrome, also called nevoid basal cell carcinoma syndrome. Clinical features of Gorlin syndrome are reported, and the relevance of hedgehog signaling pathway inhibition by oral vismodegib for maxillofacial surgeons is highlighted. In summary, progressed basal cell carcinoma lesions are virtually inoperable. Keratocystic odontogenic tumors have an aggressive behavior including rapid growth and extension into adjacent tissues. Interestingly, nearly complete regression of multiple Gorlin syndrome-associated keratocystic odontogenic tumors following treatment with vismodegib. Due to radio-hypersensitivity in Gorlin syndrome, avoidance of treatment by radiotherapy is strongly recommended for all affected individuals. Vismodegib can help in those instances where radiation is contra-indicated, or the lesions are inoperable. The effect of vismodegib on basal cell carcinomas was associated with a significant decrease in hedgehog-signaling and tumor proliferation. Vismodegib, a new and approved drug for the treatment of advanced basal cell carcinoma, is a specific oncogene inhibitor. It also seems to be effective for treatment of keratocystic odontogenic tumors and basal cell carcinomas in Gorlin syndrome, rendering the surgical resections less challenging.

Basal Cell Carcinoma of the Dorsal Hand: An Update and Comprehensive Review of the Literature.

PubMed

Loh, Tiffany Y; Rubin, Ashley G; Brian Jiang, Shang I

2016-04-01

Excessive ultraviolet radiation (UVR) exposure is the primary predisposing factor for basal cell carcinoma (BCC). However, surprisingly, BCCs occur very rarely on the dorsal hand, which is subject to intense sun exposure, and their infrequent presentation in this location suggests that other factors besides UVR may play a role in BCC pathogenesis. Because dorsal hand BCCs are uncommon, knowledge of their characteristics is limited, and more data are needed to describe their clinical presentation and treatment. To perform an updated review of the literature on the management of dorsal hand BCCs. The authors conducted a comprehensive literature review by searching the PubMed database with the key phrases "basal cell carcinoma dorsal hand," "basal cell carcinoma hand," and "basal cell carcinoma finger," and "basal cell carcinoma thumb." The authors identified 176 cases of dorsal hand BCCs in the literature, 120 of which had sufficient data for analysis. Only 4 cases were treated with Mohs micrographic surgery (MMS). The authors present 14 additional cases of dorsal hand BCCs treated with MMS. Basal cell carcinomas on the dorsal hand occur infrequently, and potential risk factors include being a male of white descent and personal history of skin cancer. Mohs micrographic surgery seems to be an effective treatment method.

Cell wall pH and auxin transport velocity

NASA Technical Reports Server (NTRS)

Hasenstein, K. H.; Rayle, D.

1984-01-01

According to the chemiosmotic polar diffusion hypothesis, auxin pulse velocity and basal secretion should increase with decreasing cell wall pH. Experiments were designed to test this prediction. Avena coleoptile sections were preincubated in either fusicoccin (FC), cycloheximide, pH 4.0, or pH 8.0 buffer and subsequently their polar transport capacities were determined. Relative to controls, FC enhanced auxin (IAA) uptake while CHI and pH 8.0 buffer reduced IAA uptake. Nevertheless, FC reduced IAA pulse velocity while cycloheximide increased velocity. Additional experiments showed that delivery of auxin to receivers is enhanced by increased receiver pH. This phenomenon was overcome by a pretreatment of the tissue with IAA. Our data suggest that while acidic wall pH values facilitate cellular IAA uptake, they do not enhance pulse velocity or basal secretion. These findings are inconsistent with the chemiosmotic hypothesis for auxin transport.

Levels of circulating soluble receptor activator of NF-κB and interleukins-1 predicting outcome of locally advanced basal cell carcinoma.

PubMed

Lin, Quan; Li, Yan; Zhang, Duo; Jin, Hongjuan

2016-12-01

Decreasing levels of cytokines are associated with better responses to therapies, while increasing levels are related to progression or recurrence and decreased survival. NF-κB's role in the cell cycle and its ubiquity are only stressed out by the evidence for the importance of activation (aberrant activation in the majority of cancers) of both canonical and non-canonical pathways in advanced basal cell carcinomas (aBCCs), a subset of basal cell carcinoma (BCC). NF-κB acts through its canonical, or classical, form activated by interleukin-1 (IL-1), regulates cytoprotective, innate, and adaptive immune responses. However, NF-κB2 often acts through its non-canonical or alternate pathway. During the two-year study period, we selected 21 patients presenting with aBCCs due to delay in accessing medical attention with an advanced form of BCCs (n = 19) and infiltrative BCCs (n = 2). Initial diagnosis of BCCs of head and neck was made clinically and verified by skin biopsy. Venous blood was drawn and serum was obtained. Samples were collected at baseline and every three days thereafter (days 3, 6, 9, etc. until surgery). Antigenes' quantities (cytokines) were determined by ELISA kits. Initially, the mean value of all cytokine subjects was significantly different related to the control group (P <0.05). Changes in serum levels of circulating soluble receptor activator of NF-κB and interleukins-1 (α and β) were observed following the surgery. Changes in serum levels of circulating soluble receptor activator of NF-κB and interleukins-1 (α and β) are evident throughout our study period and a certain regularity in its dynamics is evident as the follow-up period moves away. It was therefore concluded that measurement of these factors might be useful in predicting the overall outcome of patients with aBCCs. This study highlights the systemic effects of aBCCs, but further studies are required on this topic. © The Author(s) 2016.

Levels of circulating soluble receptor activator of NF-κB and interleukins-1 predicting outcome of locally advanced basal cell carcinoma

PubMed Central

Lin, Quan; Li, Yan; Zhang, Duo; Jin, Hongjuan

2016-01-01

Decreasing levels of cytokines are associated with better responses to therapies, while increasing levels are related to progression or recurrence and decreased survival. NF-κB’s role in the cell cycle and its ubiquity are only stressed out by the evidence for the importance of activation (aberrant activation in the majority of cancers) of both canonical and non-canonical pathways in advanced basal cell carcinomas (aBCCs), a subset of basal cell carcinoma (BCC). NF-κB acts through its canonical, or classical, form activated by interleukin-1 (IL-1), regulates cytoprotective, innate, and adaptive immune responses. However, NF-κB2 often acts through its non-canonical or alternate pathway. During the two-year study period, we selected 21 patients presenting with aBCCs due to delay in accessing medical attention with an advanced form of BCCs (n = 19) and infiltrative BCCs (n = 2). Initial diagnosis of BCCs of head and neck was made clinically and verified by skin biopsy. Venous blood was drawn and serum was obtained. Samples were collected at baseline and every three days thereafter (days 3, 6, 9, etc. until surgery). Antigenes’ quantities (cytokines) were determined by ELISA kits. Initially, the mean value of all cytokine subjects was significantly different related to the control group (P <0.05). Changes in serum levels of circulating soluble receptor activator of NF-κB and interleukins-1 (α and β) were observed following the surgery. Changes in serum levels of circulating soluble receptor activator of NF-κB and interleukins-1 (α and β) are evident throughout our study period and a certain regularity in its dynamics is evident as the follow-up period moves away. It was therefore concluded that measurement of these factors might be useful in predicting the overall outcome of patients with aBCCs. This study highlights the systemic effects of aBCCs, but further studies are required on this topic. PMID:27760847

Children's externalizing and internalizing symptoms over time: the role of individual differences in patterns of RSA responding.

PubMed

Hinnant, James Benjamin; El-Sheikh, Mona

2009-11-01

We examined associations between basal respiratory sinus arrhythmia (RSA) in conjunction with RSA regulation with the hypothesis that their interaction would explain unique variability in children's prospective adjustment 2 years later. Participants were 176 children (98 girls; 78 boys) in middle childhood. RSA regulation was assessed through social and problem-solving challenges. Parents reported on children's internalizing and externalizing symptoms. Interactions between RSA baseline and regulation to the social stressor predicted children's later internalizing symptoms. Interactions between RSA baseline and responding to the problem-solving stressor predicted children's externalizing symptoms. The highest levels of internalizing symptoms were predicted for children with both lower basal RSA and higher RSA suppression. The highest levels of externalizing symptoms were predicted for children who demonstrated lower basal RSA in conjunction with RSA augmentation. Findings highlight the importance of the contemporaneous consideration of basal RSA and RSA regulation in the prediction of developmental psychopathology symptomology.

Mapping host-species abundance of three major exotic forest pests

Treesearch

Randall S. Morin; Andrew M. Liebhold; Eugene R. Luzader; Andrew J. Lister; Kurt W. Gottschalk; Daniel B. Twardus

2005-01-01

Periodically over the last century, forests of the Eastern United States devastated by invasive pests. We used existing data to predict the geographical extent of future damage from beech bark disease (BBD), hemlock woolly adelgid (HWA), and gypsy moth. The distributions of host species of these alien pests were mapped in 1-km2 cells by interpolating host basal area/ha...

Sensitivity and specificity for detecting basal cell carcinomas in Mohs excisions with confocal fluorescence mosaicing microscopy

NASA Astrophysics Data System (ADS)

Gareau, Daniel S.; Karen, Julie K.; Dusza, Stephen W.; Tudisco, Marie; Nehal, Kishwer S.; Rajadhyaksha, Milind

2009-05-01

Recent studies have demonstrated the ability of confocal fluorescence mosaicing microscopy to rapidly detect basal cell carcinomas (BCCs) directly in thick and fresh Mohs surgical excisions. Mosaics of confocal images display large areas of tissue with high resolution and magnification equivalent to 2×, which is the standard magnification when examining pathology. Comparison of mosaics to Mohs frozen histopathology was shown to be excellent for all types of BCCs. However, comparisons in the previous studies were visual and qualitative. In this work, we report the results of a semiquantitative preclinical study in which 45 confocal mosaics are blindly evaluated for the presence (or absence) of BCC tumor. The evaluations are made by two clinicians: a senior Mohs surgeon with prior expertise in interpreting confocal images, and a novice Mohs fellow with limited experience. The blinded evaluation is compared to the gold standard of frozen histopathology. BCCs are detected with an overall sensitivity of 96.6%, specificity of 89.2%, positive predictive value of 93.0%, and negative predictive value of 94.7%. The results demonstrate the potential clinical utility of confocal mosaicing microscopy toward rapid surgical pathology at the bedside to expedite and guide surgery.

Squamous cell and basal cell carcinoma of the skin in relation to radiation therapy and potential modification of risk by sun exposure.

PubMed

Karagas, Margaret R; Nelson, Heather H; Zens, Michael S; Linet, Martha; Stukel, Therese A; Spencer, Steve; Applebaum, Katie M; Mott, Leila; Mabuchi, Kiyohiko

2007-11-01

Epidemiologic studies consistently find enhanced risk of basal cell carcinoma of the skin among individuals exposed to ionizing radiation, but it is unclear whether the radiation effect occurs for squamous cell carcinoma. It is also not known whether subgroups of individuals are at greater risk, eg, those with radiation sensitivity or high ultraviolet radiation exposure. We analyzed data from a case-control study of keratinocyte cancers in New Hampshire. Incident cases diagnosed in 1993-1995 and 1997-2000 were identified through a state-wide skin cancer surveillance system, and controls were identified through the Department of Transportation and Center for Medicare and Medicaid Service Files (n = 1121 basal cell carcinoma cases, 854 squamous cell carcinoma cases, and 1049 controls). We found an association between history of radiation treatment and basal cell carcinoma. The association was especially strong for basal cell carcinomas arising within the radiation treatment field (odds ratio = 2.6; 95% confidence interval = 1.5-4.3), and among those treated with radiation therapy before age 20 (3.4; 1.8-6.4), those whose basal cell carcinomas occurred 40 or more years after radiation treatment (3.2; 1.8-5.8), and those treated with radiation for acne (11; 2.7-49). Similar age and time patterns of risk were observed for squamous cell carcinoma, although generally with smaller odds ratios. For basal cell carcinoma, early exposure to radiation treatment was a risk factor largely among those without a history of severe sunburns, whereas for squamous cell carcinoma, radiation treatment was a risk factor primarily among those with a sun-sensitive skin type (ie, a tendency to sunburn). Radiation treatment, particularly if experienced before age 20, seems to increase the long-term risk of both basal and squamous cell carcinomas of the skin. These risks may differ by sun exposure or host response to sunlight exposure.

Skin lesion biopsy

MedlinePlus

... biopsy - skin; Skin cancer - biopsy; Melanoma - biopsy; Squamous cell cancer - biopsy; Basal cell cancer - biopsy; Mohs microsurgery ... dermatitis Infection from bacteria or fungus Melanoma Basal cell skin cancer Squamous cell skin cancer

Mammary stem cells have myoepithelial cell properties

PubMed Central

Prater, Michael D.; Petit, Valérie; Russell, I. Alasdair; Giraddi, Rajshekhar; Shehata, Mona; Menon, Suraj; Schulte, Reiner; Kalajzic, Ivo; Rath, Nicola; Olson, Michael F.; Metzger, Daniel; Faraldo, Marisa M.; Deugnier, Marie-Ange; Glukhova, Marina A.; Stingl, John

2014-01-01

Contractile myoepithelial cells dominate the basal layer of the mammary epithelium and are considered to be differentiated cells. However, we observe that up to 54% of single basal cells can form colonies when seeded into adherent culture in the presence of agents that disrupt acin-myosin interactions, and on average, 65% of the single-cell-derived basal colonies can repopulate a mammary gland when transplanted in vivo. This indicates that a high proportion of basal myoepithelial cells can give rise to a mammary repopulating unit (MRU). We demonstrate that myoepithelial cells, flow-sorted using 2 independent myoepithelial-specific reporter strategies, have MRU capacity. Using an inducible lineage tracing approach we follow the progeny of α-smooth muscle actin-expressing myoepithelial cells and show that they function as long-lived lineage-restricted stem cells in the virgin state and during pregnancy. PMID:25173976

Transducing Airway Basal Cells with a Helper-Dependent Adenoviral Vector for Lung Gene Therapy.

PubMed

Cao, Huibi; Ouyang, Hong; Grasemann, Hartmut; Bartlett, Claire; Du, Kai; Duan, Rongqi; Shi, Fushan; Estrada, Marvin; Seigel, Kyle E; Coates, Allan L; Yeger, Herman; Bear, Christine E; Gonska, Tanja; Moraes, Theo J; Hu, Jim

2018-06-01

A major challenge in developing gene-based therapies for airway diseases such as cystic fibrosis (CF) is sustaining therapeutic levels of transgene expression over time. This is largely due to airway epithelial cell turnover and the host immunogenicity to gene delivery vectors. Modern gene editing tools and delivery vehicles hold great potential for overcoming this challenge. There is currently not much known about how to deliver genes into airway stem cells, of which basal cells are the major type in human airways. In this study, helper-dependent adenoviral (HD-Ad) vectors were delivered to mouse and pig airways via intranasal delivery, and direct bronchoscopic instillation, respectively. Vector transduction was assessed by immunostaining of lung tissue sections, which revealed that airway basal cells of mice and pigs can be targeted in vivo. In addition, efficient transduction of primary human airway basal cells was verified with an HD-Ad vector expressing green fluorescent protein. Furthermore, we successfully delivered the human CFTR gene to airway basal cells from CF patients, and demonstrated restoration of CFTR channel activity following cell differentiation in air-liquid interface culture. Our results provide a strong rationale for utilizing HD-Ad vectors to target airway basal cells for permanent gene correction of genetic airway diseases.

Transdifferentiation between Luminal- and Basal-Type Cancer Cells

DTIC Science & Technology

2013-04-01

cancer patients have few choices of therapeutic agents. The MB231 cell line is a basal type cell line and is resistant to EGFR inhibitor erlotinib...mitotic inhibitor paclitaxel and DNA damaging agent cisplatin. However, over- expression of PKD1 makes the cell line sensitive to erlotinib and...approach will help to understand how PKD1 acts in basal-type cancer cells; (3) using existing small molecule inhibitors for PKD1 to treat breast cancer

Evidence for an Auditory Fovea in the New Zealand Kiwi (Apteryx mantelli)

PubMed Central

Corfield, Jeremy; Kubke, M. Fabiana; Parsons, Stuart; Wild, J. Martin; Köppl, Christine

2011-01-01

Kiwi are rare and strictly protected birds of iconic status in New Zealand. Yet, perhaps due to their unusual, nocturnal lifestyle, surprisingly little is known about their behaviour or physiology. In the present study, we exploited known correlations between morphology and physiology in the avian inner ear and brainstem to predict the frequency range of best hearing in the North Island brown kiwi. The mechanosensitive hair bundles of the sensory hair cells in the basilar papilla showed the typical change from tall bundles with few stereovilli to short bundles with many stereovilli along the apical-to-basal tonotopic axis. In contrast to most birds, however, the change was considerably less in the basal half of the epithelium. Dendritic lengths in the brainstem nucleus laminaris also showed the typical change along the tonotopic axis. However, as in the basilar papilla, the change was much less pronounced in the presumed high-frequency regions. Together, these morphological data suggest a fovea-like overrepresentation of a narrow high-frequency band in kiwi. Based on known correlations of hair-cell microanatomy and physiological responses in other birds, a specific prediction for the frequency representation along the basilar papilla of the kiwi was derived. The predicted overrepresentation of approximately 4-6 kHz matches potentially salient frequency bands of kiwi vocalisations and may thus be an adaptation to a nocturnal lifestyle in which auditory communication plays a dominant role. PMID:21887317

Polarity, cell division, and out-of-equilibrium dynamics control the growth of epithelial structures

PubMed Central

Cerruti, Benedetta; Puliafito, Alberto; Shewan, Annette M.; Yu, Wei; Combes, Alexander N.; Little, Melissa H.; Chianale, Federica; Primo, Luca; Serini, Guido; Mostov, Keith E.; Celani, Antonio

2013-01-01

The growth of a well-formed epithelial structure is governed by mechanical constraints, cellular apico-basal polarity, and spatially controlled cell division. Here we compared the predictions of a mathematical model of epithelial growth with the morphological analysis of 3D epithelial structures. In both in vitro cyst models and in developing epithelial structures in vivo, epithelial growth could take place close to or far from mechanical equilibrium, and was determined by the hierarchy of time-scales of cell division, cell–cell rearrangements, and lumen dynamics. Equilibrium properties could be inferred by the analysis of cell–cell contact topologies, and the nonequilibrium phenotype was altered by inhibiting ROCK activity. The occurrence of an aberrant multilumen phenotype was linked to fast nonequilibrium growth, even when geometric control of cell division was correctly enforced. We predicted and verified experimentally that slowing down cell division partially rescued a multilumen phenotype induced by altered polarity. These results improve our understanding of the development of epithelial organs and, ultimately, of carcinogenesis. PMID:24145168

Live Imaging at the Onset of Cortical Neurogenesis Reveals Differential Appearance of the Neuronal Phenotype in Apical versus Basal Progenitor Progeny

PubMed Central

Attardo, Alessio; Calegari, Federico; Haubensak, Wulf; Wilsch-Bräuninger, Michaela; Huttner, Wieland B.

2008-01-01

The neurons of the mammalian brain are generated by progenitors dividing either at the apical surface of the ventricular zone (neuroepithelial and radial glial cells, collectively referred to as apical progenitors) or at its basal side (basal progenitors, also called intermediate progenitors). For apical progenitors, the orientation of the cleavage plane relative to their apical-basal axis is thought to be of critical importance for the fate of the daughter cells. For basal progenitors, the relationship between cell polarity, cleavage plane orientation and the fate of daughter cells is unknown. Here, we have investigated these issues at the very onset of cortical neurogenesis. To directly observe the generation of neurons from apical and basal progenitors, we established a novel transgenic mouse line in which membrane GFP is expressed from the beta-III-tubulin promoter, an early pan-neuronal marker, and crossed this line with a previously described knock-in line in which nuclear GFP is expressed from the Tis21 promoter, a pan-neurogenic progenitor marker. Mitotic Tis21-positive basal progenitors nearly always divided symmetrically, generating two neurons, but, in contrast to symmetrically dividing apical progenitors, lacked apical-basal polarity and showed a nearly randomized cleavage plane orientation. Moreover, the appearance of beta-III-tubulin–driven GFP fluorescence in basal progenitor-derived neurons, in contrast to that in apical progenitor-derived neurons, was so rapid that it suggested the initiation of the neuronal phenotype already in the progenitor. Our observations imply that (i) the loss of apical-basal polarity restricts neuronal progenitors to the symmetric mode of cell division, and that (ii) basal progenitors initiate the expression of neuronal phenotype already before mitosis, in contrast to apical progenitors. PMID:18545663

Gap junctions and other mechanisms of cell-cell communication regulate basal insulin secretion in the pancreatic islet.

PubMed

Benninger, R K P; Head, W Steven; Zhang, Min; Satin, Leslie S; Piston, David W

2011-11-15

Cell-cell communication in the islet of Langerhans is important for the regulation of insulin secretion. Gap-junctions coordinate oscillations in intracellular free-calcium ([Ca(2+)](i)) and insulin secretion in the islet following elevated glucose. Gap-junctions can also ensure that oscillatory [Ca(2+)](i) ceases when glucose is at a basal levels. We determine the roles of gap-junctions and other cell-cell communication pathways in the suppression of insulin secretion under basal conditions. Metabolic, electrical and insulin secretion levels were measured from islets lacking gap-junction coupling following deletion of connexion36 (Cx36(-/-)), and these results were compared to those obtained using fully isolated β-cells. K(ATP) loss-of-function islets provide a further experimental model to specifically study gap-junction mediated suppression of electrical activity. In isolated β-cells or Cx36(-/-) islets, elevations in [Ca(2+)](i) persisted in a subset of cells even at basal glucose. Isolated β-cells showed elevated insulin secretion at basal glucose; however, insulin secretion from Cx36(-/-) islets was minimally altered. [Ca(2+)](i) was further elevated under basal conditions, but insulin release still suppressed in K(ATP) loss-of-function islets. Forced elevation of cAMP led to PKA-mediated increases in insulin secretion from islets lacking gap-junctions, but not from islets expressing Cx36 gap junctions. We conclude there is a redundancy in how cell-cell communication in the islet suppresses insulin release. Gap junctions suppress cellular heterogeneity and spontaneous [Ca(2+)](i) signals, while other juxtacrine mechanisms, regulated by PKA and glucose, suppress more distal steps in exocytosis. Each mechanism is sufficiently robust to compensate for a loss of the other and still suppress basal insulin secretion.

Dual effect of cell-cell contact disruption on cytosolic calcium and insulin secretion.

PubMed

Jaques, Fabienne; Jousset, Hélène; Tomas, Alejandra; Prost, Anne-Lise; Wollheim, Claes B; Irminger, Jean-Claude; Demaurex, Nicolas; Halban, Philippe A

2008-05-01

Cell-to-cell interactions play an important role in insulin secretion. Compared with intact islets, dispersed pancreatic beta-cells show increased basal and decreased glucose-stimulated insulin secretion. In this study, we used mouse MIN6B1 cells to investigate the mechanisms that control insulin secretion when cells are in contact with each other or not. RNAi-mediated silencing of the adhesion molecule E-cadherin in confluent cells reduced glucose-stimulated secretion to the levels observed in isolated cells but had no impact on basal secretion. Dispersed cells presented high cytosolic Ca(2+) activity, depolymerized cytoskeleton and ERK1/2 activation in low glucose conditions. Both the increased basal secretion and the spontaneous Ca(2+) activity were corrected by transient removal of Ca(2+) or prolonged incubation of cells in low glucose, a procedure that restored the ability of dispersed cells to respond to glucose (11-fold stimulation). In conclusion, we show that dispersed pancreatic beta-cells can respond robustly to glucose once their elevated basal secretion has been corrected. The increased basal insulin secretion of dispersed cells is due to spontaneous Ca(2+) transients that activate downstream Ca(2+) effectors, whereas engagement of cell adhesion molecules including E-cadherin contributes to the greater secretory response to glucose seen in cells with normal intercellular contacts.

СD44+/CD24- markers of cancer stem cells in patients with breast cancer of different molecular subtypes.

PubMed

Chekhun, S V; Zadvorny, T V; Tymovska, Yu O; Anikusko, M F; Novak, O E; Polishchuk, L Z

2015-03-01

To determine frequency of tumors with immunohistochemical markers of cancer stem cells (CSC) CD44+/CD24- in patients with breast cancer (BC) of different molecular subtype and to evaluate their prognostic value. Surgical material of 132 patients with BC stage I-II, age from 23 to 75 years, mean age - 50.2 ± 3.1 years was studied. Clinical, immunohistochemical (expression CD44+/CD24-), morphological, statistical. BC is characterized by heterogeneity of molecular subtypes and expression of markers (CD44+/CD24-). Immunohistochemical study of expression of CSC markers in surgical material has detected their expression in 34 (25.4%) patients with BC of different molecular subtypes. The highest frequency of cells with expression of CSC marker was observed in patients with basal molecular subtype (44.8% patients). Most of BC patients with phenotype CD44+/CD24 had stage I of tumor process (34.3%). Statistical processing of data has showen that Yule colligation coefficient equaled 0.28 (р > 0.05) that argues poor correlation between stage of tumor process and number of tumors with positive expression of CSC markers. Statistical processing of data has showen high correlation between presence of cells with expression of CSC markers and metastases of BC in regional lymph nodes (Yule colligation coefficient equals 0.943; р < 0.5). Difference in overall survival of patients with BC of basal molecular subtype depending on expression of CSC CD44+/CD24- markers was detected. Survival of patients with basal BC was reliably higher at lack in tumors of cells with CSC markers CD44+/CD24- and, correspondingly, lower at presence of such cells (р < 0.05). In patients with BC of luminal (A and B), HER-2-positive subtypes, significant change in survival of patients depending on expression of CSC markers was not determined (р > 0.05). Significance of tumor cells with markers CD44+/CD24- within the limits of molecular subtype of BC may be additional criterion for advanced biological characteristic of BC, and in patients with BC of basal molecular subtype - for predictive evaluation of individual potential of tumor to aggressive clinical course.

Manifestations of Gorlin-Goltz syndrome.

PubMed

Larsen, Anne Kristine; Mikkelsen, Dorthe Bisgaard; Hertz, Jens Michael; Bygum, Anette

2014-05-01

Gorlin-Goltz syndrome is an uncommon hereditary condition caused by mutations in the PTCH1 gene causing a wide range of developmental abnormalities. Multiple basal cell carcinomas, palmoplantar pits and jaw cysts are cardinal features. Many clinicians are unfamiliar with the different manifestations and the fact that patients are especially sensitive to ionizing radiation. This was a retrospective analysis of patients with Gorlin-Goltz syndrome seen at the Department of Dermatology and Allergy Centre or at Department of Plastic Surgery, Odense University Hospital, Denmark, in the period from 1994 to 2013. A total of 17 patients from eight families fulfilled the diagnostic criteria. In all, 14 patients had basal cell carcinomas, 12 patients had jaw cysts and ten patients had calcification of the falx cerebri. Other clinical features were frontal bossing, kyphoscoliosis, rib anomalies, coalitio, cleft lip/palate, eye anomalies, milia and syndactyly. In one family, medulloblastoma and astrocytoma occurred. Traditional treatment principles of basal cell carcinomas were used including radiotherapy performed in six patients. PTCH1 mutations were identified in five families and none of these mutations had previously been described. The patient cohort illustrates classic and rare disease manifestations. It is necessary to remind clinicians that radiation therapy in Gorlin-Goltz syndrome is relatively contraindicated. Today, mutation analysis can be used for confirmation of the diagnosis and for predictive genetic testing. Patients should be offered genetic counselling and life-long surveillance. not relevant. not relevant.

Elevated YAP and its downstream targets CCN1 and CCN2 in basal cell carcinoma: impact on keratinocyte proliferation and stromal cell activation.

PubMed

Quan, Taihao; Xu, Yiru; Qin, Zhaoping; Robichaud, Patrick; Betcher, Stephanie; Calderone, Ken; He, Tianyuan; Johnson, Timothy M; Voorhees, John J; Fisher, Gary J

2014-04-01

Yes-associated protein (YAP) is a transcriptional co-activator of hippo signaling pathway, which plays an important role in organ size control and tumorigenesis. Here we report that YAP and its downstream transcriptional targets CCN1 and CCN2 are markedly elevated in keratinocytes in human skin basal cell carcinoma tumor islands. In human keratinocytes, knockdown of YAP significantly reduced expression of CCN1 and CCN2, and repressed proliferation and survival. This inhibition of proliferation and survival was rescued by restoration of CCN1 expression, but not by CCN2 expression. In basal cell carcinoma stroma, CCN2-regulated genes type I collagen, fibronectin, and α-smooth muscle actin were highly expressed. Furthermore, atomic force microscopy revealed increased tissue stiffness in basal cell carcinoma stroma compared to normal dermis. These data provide evidence that up-regulation of YAP in basal cell carcinoma impacts both aberrant keratinocyte proliferation, via CCN1, and tumor stroma cell activation and stroma remodeling, via CCN2. Targeting YAP and/or CCN1 and CCN2 may provide clinical benefit in basal cell carcinoma. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

[Exenteration of the Orbit for Basal Cell Carcinoma].

PubMed

Furdová, A; Horkovičová, K; Krčová, I; Krásnik, V

2015-08-01

Primary treatment of basal cell carcinoma of the lower eyelid and the inner corner is essentially surgical, but advanced lesions require extensive surgical interventions. In some cases it is necessary to continue with the mutilating surgery--exenteration of the orbit. In this work we evaluate the indications of radical solutions in patients with basal cell carcinoma invading the orbit and the subsequent possibility for individually made prosthesis to cover the defect of the cavity. Indications to exenteration of the orbit in patients with basal cell carcinoma findings in 2008-2013. Case report of 2 patients. In period 2008-20013 at the Dept. of Ophthalmology, Comenius University in Bratislava totally 221 patients with histologically confirmed basal cell carcinoma of the eyelids and the inner corner were treated. In 5 cases (2.7 %) with infiltration of the orbit the radical surgical procedure, exenteration was necessary. In 3 patients exenteration was indicated as the first surgical procedure in the treatment of basal cell carcinoma, since they had never visited ophthalmologist before only at in the stage of infiltration of the orbit (stage T4). In one case was indicated exenteration after previous surgical interventions and relapses. After healing the cavity patients got individually prepared epithesis. Surgical treatment of basal cell carcinoma involves the radical removal of the neoplasm entire eyelid and stage T1 or T2 can effectively cure virtually all tumors with satisfactory cosmetic and functional results. In advanced stages (T4 stage) by infiltrating the orbit by basal cell carcinoma exenteration of the orbit is necessary. This surgery is a serious situation for the patient and also for his relatives. Individually made prosthesis helps the patient to be enrolled to the social environment.

Quiz: Test Your Skin Cancer IQ

MedlinePlus

... three main types of skin cancer: basal cell carcinoma, squamous cell carcinoma, and melanoma. They can develop from the uncontrolled growth of three different types of skin cells: basal cells, squamous cells, and melanocytes, respectively. A is the correct answer. ...

Number of Langerhans cells is decreased in premalignant keratosis and skin cancers.

PubMed

Shevchuk, Z; Filip, A; Shevchuk, V; Kashuba, E

2014-03-01

It was shown earlier that a number of CD207 positive Langerhans cells was lower in basal cell carcinomas than in the normal epidermis. Moreover, benign skin lesions presented a higher number of Langerhans cells when they were compared to malignant tumors. To count Langerhans cells, assessing expression levels of CD1A and CD207 markers in actinic keratosis, basal and squamous cell carcinomas, compared with the normal skin. Comparison of Langerhans cells might give a valuable prognostic marker for skin cancer. Immunohistochemistry and methods of statistics were used. Expression of CD1A and CD207 markers was assessed in tumor samples of actinic keratosis, cutaneous basal and squamous cell carcinomas, in comparison with the normal skin. In each cohort there were 40 patients (and 11 healthy individuals). We have shown that the number of Langerhans cells is considerably lower in cutaneous basal and squamous cell carcinomas, compared with their number in the normal skin (p < 0.0001). CD1A expression correlated with CD207 expression only in the control group. There was no correlation in actinic keratosis, basal and squamous cell carcinoma. This may suggest an alteration of Langerhans cells phenotype in skin neoplastic diseases, making the number of Langerhans cells a valuable prognostic factor for skin tumors.

Distribution and ultrastructural characteristics of dark cells in squamous metaplasias of the respiratory tract epithelium.

PubMed Central

Klein-Szanto, A. J.; Nettesheim, P.; Pine, A.; Martin, D.

1981-01-01

Dark epithelial basal cells were found in both carcinogen-induced and non-carcinogen-induced squamous metaplasias of the tracheal epithelium. Formaldehyde-induced squamous metaplasias exhibited 4% dark cells in the basal layer. Metaplasias induced by vitamin A deficiency and those induced by dimethylbenz(alpha)anthracene (DMBA) without atypia showed 18--20% basal dark cells. DMBA-induced metaplasias with moderate to severe atypia exhibited 50% basal dark cells. The labeling index of basal cells in metaplastic epithelia, regardless of the inducing agent, was 16--18%, ie, the same as that of the normal esophageal stratified squamous epithelium. The percentage of labeled dark basal cells per total dark cell population was approximately 19% in the non-carcinogen-induced metaplasias and in the DMBA-induced metaplasias without atypia. In the atypical metaplasias induced by DMA this percentage increased to 26. On the basis of ultrastructural observations, five types of dark epithelial cells could be distinguished in the metaplastic epithelia: Type I (ovoid or fusiform dark cell with abundant cytoplasmic filaments, desmosomes, and free ribosomes--dark keratinocyte type); Type II (ovoid or spherical small cell with scant cytoplasm with few organelles--basal respiratory type); Type III (irregular or ovoid, few cytoplasmic filaments and organelles and desmosomes, extremely abundant free ribosomes--dedifferentiated type); Type IV (fusiform or ovoid, large mitochondria, prominent ergastoplasm, secretion droplets--mucous cell type); and type V (irregular shape, organelle remnants, vacuoles, pyknotic nuclei--involutional-cell type). Type I was the predominant cell type in formaldehyde-induced metaplasias and was also commonly seen in DMBA-induced metaplasias without atypia. Type II predominated in metaplasias induced by vitamin A deficiency. Type III was seen in DMBA-induced metaplasias and was the predominant cell type in the atypical epithelial alterations. Type IV cells occurred only in the latter, and Type V cells were occasionally seen in formaldehyde- as well as in DMBA-induced atypical metaplasias. Each type of squamous metaplasia could thus be recognized by a determined numerical distribution of dark cells in the basal layer and a specific pattern of distribution of the ultrastructurally defined dark cell categories. Images Figure 3 Figure 4 Figure 5 Figure 1 Figure 2 Figure 6 Figure 7 PMID:6786102

Pigmented Basal cell carcinoma of nipple and areola in a male breast - a case report with review of literature.

PubMed

Kalyani, R; Vani, B R; Srinivas, Murthy V; Veda, P

2014-03-01

Basal cell carcinoma is a common skin cancer worldwide. However basal cell carcinoma of nipple and areola complex is rare, commonly seen in males in elderly age group. The tumor has aggressive behavior with increased tendency for metastasis. We present a case in a 78 year male in the left breast.

Cytotoxicity assays with fish cells as an alternative to the acute lethality test with fish.

PubMed

Segner, Helmut

2004-10-01

In ecotoxicology, in vitro assays with fish cells are currently applied for mechanistic studies, bioanalytical purposes and toxicity screening. This paper discusses the potential of cytotoxicity assays with fish cells to reduce, refine or replace acute lethality tests using fish. Basal cytotoxicity data obtained with fish cell lines or fish primary cell cultures show a reasonable to good correlation with lethality data from acute toxicity tests, with the exception of compounds that exert a specific mode of toxic action. Basal cytotoxicity data from fish cell lines also correlate well with cytotoxicity data from mammalian cell lines. However, both the piscine and mammalian in vitro assays are clearly less sensitive than the fish test. Therefore, in vivo LC50 values (concentrations of the test compounds that are lethal to 50% of the fish in the experiment within 96 hours) currently cannot be predicted from in vitro values. This in vitro-in vivo difference in sensitivity appears to be true for both fish cell lines and mammalian cell lines. Given the good in vitro-in vivo correlation in toxicity ranking, together with the clear-cut difference in sensitivity, the role of cytotoxicity assays in a tiered alternative testing strategy could be in priority setting in relation to toxic hazard and in the toxicity classification of chemicals and environmental samples.

Rootletin interacts with C-Nap1 and may function as a physical linker between the pair of centrioles/basal bodies in cells.

PubMed

Yang, Jun; Adamian, Michael; Li, Tiansen

2006-02-01

Rootletin, a major structural component of the ciliary rootlet, is located at the basal bodies and centrosomes in ciliated and nonciliated cells, respectively. Here we investigated its potential role in the linkage of basal bodies/centrioles and the mechanism involved in such linkages. We show that rootletin interacts with C-Nap1, a protein restricted at the ends of centrioles and functioning in centrosome cohesion in interphase cells. Their interaction in vivo is supported by their colocalization at the basal bodies/centrioles and coordinated association with the centrioles during the cell cycle. Ultrastructural examinations demonstrate that rootletin fibers connect the basal bodies in ciliated cells and are present both at the ends of and in between the pair of centrioles in nonciliated cells. The latter finding stands in contrast with C-Nap1, which is present only at the ends of the centrioles. Transient expression of C-Nap1 fragments dissociated rootletin fibers from the centrioles, resulting in centrosome separation in interphase. Overexpression of rootletin in cells caused multinucleation, micronucleation, and irregularity of nuclear shape and size, indicative of defects in chromosome separation. These data suggest that rootletin may function as a physical linker between the pair of basal bodies/centrioles by binding to C-Nap1.

Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade.

PubMed

Lipson, Evan J; Lilo, Mohammed T; Ogurtsova, Aleksandra; Esandrio, Jessica; Xu, Haiying; Brothers, Patricia; Schollenberger, Megan; Sharfman, William H; Taube, Janis M

2017-01-01

Monoclonal antibodies that block immune regulatory proteins such as programmed death-1 (PD-1) have demonstrated remarkable efficacy in controlling the growth of multiple tumor types. Unresectable or metastatic basal cell carcinoma, however, has largely gone untested. Because PD-Ligand-1 (PD-L1) expression in other tumor types has been associated with response to anti-PD-1, we investigated the expression of PD-L1 and its association with PD-1 expression in the basal cell carcinoma tumor microenvironment. Among 40 basal cell carcinoma specimens, 9/40 (22%) demonstrated PD-L1 expression on tumor cells, and 33/40 (82%) demonstrated PD-L1 expression on tumor-infiltrating lymphocytes and associated macrophages. PD-L1 was observed in close geographic association to PD-1+ tumor infiltrating lymphocytes. Additionally, we present, here, the first report of an objective anti-tumor response to pembrolizumab (anti-PD-1) in a patient with metastatic PD-L1 (+) basal cell carcinoma, whose disease had previously progressed through hedgehog pathway-directed therapy. The patient remains in a partial response 14 months after initiation of therapy. Taken together, our findings provide a rationale for testing anti-PD-1 therapy in patients with advanced basal cell carcinoma, either as initial treatment or after acquired resistance to hedgehog pathway inhibition.

Constitutive NOTCH3 Signaling Promotes the Growth of Basal Breast Cancers.

PubMed

Choy, Lisa; Hagenbeek, Thijs J; Solon, Margaret; French, Dorothy; Finkle, David; Shelton, Amy; Venook, Rayna; Brauer, Matthew J; Siebel, Christian W

2017-03-15

Notch ligands signal through one of four receptors on neighboring cells to mediate cell-cell communication and control cell fate, proliferation, and survival. Although aberrant Notch activation has been implicated in numerous malignancies, including breast cancer, the importance of individual receptors in distinct breast cancer subtypes and the mechanisms of receptor activation remain unclear. Using a novel antibody to detect active NOTCH3, we report here that NOTCH3 signals constitutively in a panel of basal breast cancer cell lines and in more than one third of basal tumors. Selective inhibition of individual ligands revealed that this signal does not require canonical ligand induction. A NOTCH3 antagonist antibody inhibited growth of basal lines, whereas a NOTCH3 agonist antibody enhanced the transformed phenotype in vitro and in tumor xenografts. Transcriptomic analyses generated a Notch gene signature that included Notch pathway components, the oncogene c-Myc , and the mammary stem cell regulator Id4 This signature drove clustering of breast cancer cell lines and tumors into the common subtypes and correlated with the basal classification. Our results highlight an unexpected ligand-independent induction mechanism and suggest that constitutive NOTCH3 signaling can drive an oncogenic program in a subset of basal breast cancers. Cancer Res; 77(6); 1439-52. ©2017 AACR . ©2017 American Association for Cancer Research.

Basal-like Breast Cancers: From Pathology to Biology and Back Again.

PubMed

Gusterson, Barry; Eaves, Connie J

2018-06-05

Human breast cancers referred to as "basal-like" are of interest because they lack effective therapies and their biology is poorly understood. The term basal-like derives from studies demonstrating tumor gene expression profiles that include some transcripts characteristic of the basal cells of the normal adult human mammary gland and others associated with a subset of normal luminal cells. Elucidating the mechanisms responsible for the profiles of basal-like tumors is an active area of investigation. More refined molecular analysis of patients' samples and genetic strategies to produce breast cancers de novo from defined populations of normal mouse mammary cells have served as complementary approaches to identify relevant pathway alterations. However, both also have limitations. Here, we review some of the underlying reasons, including the unifying concept that some normal luminal cells have both luminal and basal features, as well as some emerging new avenues of investigation. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Efficacy of Vismodegib (Erivedge) for Basal Cell Carcinoma Involving the Orbit and Periocular Area.

PubMed

Demirci, Hakan; Worden, Francis; Nelson, Christine C; Elner, Victor M; Kahana, Alon

2015-01-01

Evaluate the effectiveness of vismodegib in the management of basal cell carcinoma with orbital extension and/or extensive periocular involvement. Retrospective chart review of 6 consecutive patients with biopsy-proven orbital basal cell carcinoma and 2 additional patients with extensive periocular basal cell carcinoma who were treated with oral vismodegib (150 mg/day) was performed. Basal cell carcinoma extended in the orbit in 6 of 8 patients (involving orbital bones in 1 patient), and 2 of 8 patients had extensive periocular involvement (1 with basal cell nevus syndrome). Vismodegib therapy was the only treatment in 6 patients, off-label neoadjuvant in 1 patient, and adjuvant treatment in 1 patient. Orbital tumors in all 4 patients who received vismodegib as sole treatment showed partial response with a mean 83% shrinkage in tumor size after a median of 7 months of therapy. In the 2 patients receiving vismodegib as neoadjuvant or adjuvant therapies, there was complete response after a median of 7 months of therapy and no evidence of clinical recurrence after discontinuing therapy for a median of 15 months. The 2 patients with extensive periocular involvement experienced complete clinical response after a median 14 months of treatment. During treatment, the most common side effects were muscle spasm (75%) followed by alopecia (50%), dysgeusia (25%), dysosmia, and episodes of diarrhea and constipation (13%). Basal cell carcinoma with orbital extension and extensive periocular involvement responds to vismodegib therapy. The long-term prognosis remains unknown, and additional prospective studies are indicated.

Toxicants target cell junctions in the testis: Insights from the indazole-carboxylic acid model

PubMed Central

Cheng, C Yan

2014-01-01

There are numerous types of junctions in the seminiferous epithelium which are integrated with, and critically dependent on the Sertoli cell cytoskeleton. These include the basal tight junctions between Sertoli cells that form the main component of the blood–testis barrier, the basal ectoplasmic specializations (basal ES) and basal tubulobulbar complexes (basal TBC) between Sertoli cells; as well as apical ES and apical TBC between Sertoli cells and the developing spermatids that orchestrate spermiogenesis and spermiation. These junctions, namely TJ, ES, and TBC interact with actin microfilament-based cytoskeleton, which together with the desmosomal junctions that interact with the intermediate filament-based cytoskeleton plus the highly polarized microtubule-based cytoskeleton are working in concert to move spermatocytes and spermatids between the basal and luminal aspect of the seminiferous epithelium. In short, these various junctions are structurally complexed with the actin- and microtubule-based cytoskeleton or intermediate filaments of the Sertoli cell. Studies have shown toxicants (e.g., cadmium, bisphenol A (BPA), perfluorooctanesulfonate (PFOS), phthalates, and glycerol), and some male contraceptives under development (e.g., adjudin, gamendazole), exert their effects, at least in part, by targeting cell junctions in the testis. The disruption of Sertoli–Sertoli cell and Sertoli–germ cell junctions, results in the loss of germ cells from the seminiferous epithelium. Adjudin, a potential male contraceptive under investigation in our laboratory, produces loss of spermatids from the seminiferous tubules through disruption of the Sertoli cell spermatid junctions and disruption of the Sertoli cell cytoskeleton. The molecular and structural changes associated with adjudin administration are described, to provide an example of the profile of changes caused by disturbance of Sertoli-germ cell and also Sertoli cell-cell junctions. PMID:26413399

Vismodegib (ERIVEDGE°) In basal cell carcinoma: too many unknowns.

PubMed

2015-01-01

Basal cell carcinomas are the most common skin cancers. They are usually localised and carry a good prognosis. There is no standard treatment for the rare patients with metastatic basal cell carcinoma or very extensive basal cell carcinoma for whom surgery or radiotherapy is inappropriate. Vismodegib, a cytotoxic drug, is claimed to prevent tumour growth by inhibiting a pathway involved in tissue repair and embryogenesis. It has been authorised in the European Union for patients with metastatic or locally advanced and extensive basal cell carcinoma. Clinical evaluation of vismodegib is based on a non-comparative clinical trial involving 104 patients, providing only weak evidence. Twenty-one months after the start of the trial, 7 patients with metastases (21%) and 6 patients with advanced basal cell carcinoma (10%) had died. Given the lack of a placebo group, there is no way of knowing whether vismodegib had any effect, positive or negative, on survival. There were no complete responses among patients with metastases, but about one-third of them had partial responses. Among the 63 patients with locally advanced basal cell carcinoma, there were 14 complete responses and 16 partial responses. The recurrence rate in patients with complete responses was not reported. Similar results were reported in two other uncontrolled trials available in mid-2014. Vismodegib has frequent and sometimes serious adverse effects, including muscle spasms, fatigue and severe hyponatraemia. Cases of severe weight loss, alopecia, ocular disorders, other cancers (including squamous cell carcinoma) and anaemia have also been reported. More data are needed on possible hepatic and cardiovascular adverse effects. A potent teratogenic effect was seen in experimental animals. As vismodegib enters semen, contraception is mandatory for both men (condoms) and women. In practice, vismodegib has frequent and varied adverse effects, some of which are serious, while its benefits are poorly documented. Vismodegib should only be proposed to patients in whom basal cell cancer markedly undermines quality of life, and only in the context of clinical research.

Pigmented Basal Cell Carcinoma of Nipple and Areola in a Male Breast - A Case Report with Review of Literature

PubMed Central

Kalyani, R.; Vani, B. R.; Srinivas, Murthy V.; Veda, P.

2014-01-01

Basal cell carcinoma is a common skin cancer worldwide. However basal cell carcinoma of nipple and areola complex is rare, commonly seen in males in elderly age group. The tumor has aggressive behavior with increased tendency for metastasis. We present a case in a 78 year male in the left breast. PMID:24711752

Use of tanning devices and risk of basal cell and squamous cell skin cancers.

PubMed

Karagas, Margaret R; Stannard, Virginia A; Mott, Leila A; Slattery, Mary Jo; Spencer, Steven K; Weinstock, Martin A

2002-02-06

Use of artificial tanning devices that emit UV radiation, such as tanning lamps and tanning beds, has become increasingly popular in the United States. Although an excess risk of nonmelanoma skin cancers might be predicted from this exposure, little epidemiologic data exist. We conducted a population-based, case-control study that included 603 basal cell carcinoma (BCC) case patients, 293 squamous cell carcinoma (SCC) case patients, and 540 control subjects. Study participants were interviewed in person to obtain information on tanning device use, sun exposure history, sun sensitivity, and other risk factors for skin cancer. Overall, any use of tanning devices was associated with odds ratios of 2.5 (95% confidence interval [CI] = 1.7 to 3.8) for SCC and 1.5 (95% CI = 1.1 to 2.1) for BCC. Adjustment for history of sunburns, sunbathing, and sun exposure did not affect our results. Our findings suggest that the use of tanning devices may contribute to the incidence of nonmelanoma skin cancers. They highlight the need to further evaluate the potential risks of BCC and SCC that are associated with tanning lamp exposure and the appropriate public health response.

Skin Diseases: Skin Health and Skin Diseases

MedlinePlus

... The two most common types are basal cell cancer and squamous cell cancer. Melanoma, a more serious type of skin ... The two most common types are basal cell cancer and squamous cell cancer. They usually form on the head, face, ...

RNA Helicase DDX5 Regulates MicroRNA Expression and Contributes to Cytoskeletal Reorganization in Basal Breast Cancer Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Daojing; Huang, Jing; Hu, Zhi

RNA helicase DDX5 (also p68) is involved in all aspects of RNA metabolism and serves as a transcriptional co-regulator, but its functional role in breast cancer remains elusive. Here, we report an integrative biology study of DDX5 in breast cancer, encompassing quantitative proteomics, global MicroRNA profiling, and detailed biochemical characterization of cell lines and human tissues. We showed that protein expression of DDX5 increased progressively from the luminal to basal breast cancer cell lines, and correlated positively with that of CD44 in the basal subtypes. Through immunohistochemistry analyses of tissue microarrays containing over 200 invasive human ductal carcinomas, we observedmore » that DDX5 was upregulated in the majority of malignant tissues, and its expression correlated strongly with those of Ki67 and EGFR in the triple-negative tumors. We demonstrated that DDX5 regulated a subset of MicroRNAs including miR-21 and miR-182 in basal breast cancer cells. Knockdown of DDX5 resulted in reorganization of actin cytoskeleton and reduction of cellular proliferation. The effects were accompanied by upregulation of tumor suppressor PDCD4 (a known miR-21 target); as well as upregulation of cofilin and profilin, two key proteins involved in actin polymerization and cytoskeleton maintenance, as a consequence of miR-182 downregulation. Treatment with miR-182 inhibitors resulted in morphologic phenotypes resembling those induced by DDX5 knockdown. Using bioinformatics tools for pathway and network analyses, we confirmed that the network for regulation of actin cytoskeleton was predominantly enriched for the predicted downstream targets of miR-182. Our results reveal a new functional role of DDX5 in breast cancer via the DDX5→miR-182→actin cytoskeleton pathway, and suggest the potential clinical utility of DDX5 and its downstream MicroRNAs in the theranostics of breast cancer.« less

The expression patterns of aquaporin 9, vacuolar H+-ATPase, and cytokeratin 5 in the epididymis of the common vampire bat.

PubMed

Castro, Mariana M; Kim, Bongki; Hill, Eric; Fialho, Maria C Q; Puga, Luciano C H P; Freitas, Mariella B; Breton, Sylvie; Machado-Neves, Mariana

2017-01-01

Desmodus rotundus is a vampire bat species that inhabits Latin America. Some basic aspects of this species' biology are still unknown, as the histophysiological characteristics of the male reproductive tract. Our study has focused on its epididymis, which is an important organ for performing a variety of functions, especially the sperm maturation and storage. The aim of this study was to identify principal, narrow, clear, and basal cells using cell-specific markers such as aquaporin 9 (AQP9), vacuolar H + -ATPase (V-ATPase), and cytokeratin 5 (KRT5). Principal cells were labeled by AQP9 from initial segment to cauda region in their stereocilia. They were shown with a columnar shape, whereas V-ATPase-rich cells were identified with a goblet-shaped body along the entire epididymis, including the initial segment, which were named as clear cells. Pencil-shaped V-ATPase-rich cells (narrow cells) were not detected in the initial segment of the bat epididymis, unlike in the rodent. Basal cells were labeled by KRT5 and were located at the basal portion of the epithelium forming a dense network. However, no basal cells with a luminal-reaching body extension were observed in the bat epididymis. In summary, epithelial cells were identified by their specific markers in the vampire bat epididymis. Principal and basal cells were labeled by AQP9 and KRT5, respectively. Narrow cells were not observed in the vampire bat epididymis, whereas clear cells were identified by V-ATPase labeling along the entire duct in a goblet-shaped body. In addition, no luminal-reaching basal cells were observed in the vampire bat epididymis.

A system for predicting the amount of Phellinus (Fomes) igniarius rot in trembling aspen stands

Treesearch

Robert L. Anderson; Arthur L. Jr. Schipper

1978-01-01

The occurrence of Phellinus (Fomes) igniarius white trunk rot in 45- to 50-year-old trembling aspen stands can be predicted by applying a constant to the stand basal area with P. igniarius conks to estimate the total basal area with P. igniarius rot. Future decay projections can be made by reapplying the basal area of hidden decay for each 6 years projected. This paper...

A case illustrating successful eradication of recurrent, aggressive basal cell carcinoma located in a scar with vismodegib.

PubMed

Lucero, Olivia M; Fitzmaurice, Sarah; Thompson, Curtis; Leitenberge, Justin

2018-02-15

Vismodegib is a small molecule inhibitor of the Hedgehog signaling pathway that has shown efficacy in the control of locally advanced or metastatic basal cell carcinoma, although proof of its effectiveness in the elimination of aggressive tumors is lacking. We report a case and provide complete histological evidence of a 69-year-old gentleman who presented with a recurrent, infiltrative, and sclerosing (morpheiform) basal cell carcinoma on his left upper lip that was entirely eradicated with a three-month course of vismodegib 150 mg daily. Complete histologic clearance of a tumor in a recurrent, infiltrative, and sclerosing basal cell carcinoma with vismodegib is uncommon.

Vismodegib in patients with advanced basal cell carcinoma (STEVIE): a pre-planned interim analysis of an international, open-label trial.

PubMed

Basset-Seguin, Nicole; Hauschild, Axel; Grob, Jean-Jacques; Kunstfeld, Rainer; Dréno, Brigitte; Mortier, Laurent; Ascierto, Paolo A; Licitra, Lisa; Dutriaux, Caroline; Thomas, Luc; Jouary, Thomas; Meyer, Nicolas; Guillot, Bernard; Dummer, Reinhard; Fife, Kate; Ernst, D Scott; Williams, Sarah; Fittipaldo, Alberto; Xynos, Ioannis; Hansson, Johan

2015-06-01

The Hedgehog pathway inhibitor vismodegib has shown clinical benefit in patients with advanced basal cell carcinoma and is approved for treatment of patients with advanced basal cell carcinoma for whom surgery is inappropriate. STEVIE was designed to assess the safety of vismodegib in a situation similar to routine practice, with a long follow-up. In this multicentre, open-label trial, adult patients with histologically confirmed locally advanced basal cell carcinoma or metastatic basal cell carcinoma were recruited from regional referral centres or specialist clinics. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and adequate organ function. Patients with locally advanced basal cell carcinoma had to have been deemed ineligible for surgery. All patients received 150 mg oral vismodegib capsules once a day on a continuous basis in 28-day cycles. The primary objective was safety (incidence of adverse events until disease progression or unacceptable toxic effects), with assessments on day 1 of each treatment cycle (28 days) by principal investigator and coinvestigators at the site. Efficacy variables were assessed as secondary endpoints. The safety evaluable population included all patients who received at least one dose of study drug. Patients with histologically confirmed basal cell carcinoma who received at least one dose of study drug were included in the efficacy analysis. An interim analysis was pre-planned after 500 patients achieved 1 year of follow-up. This trial is registered with ClinicalTrials.gov, number NCT01367665. The study is still ongoing. Between June 30, 2011, and Nov 6, 2014, we enrolled 1227 patients. At clinical cutoff (Nov 6, 2013), 499 patients (468 with locally advanced basal cell carcinoma and 31 with metastatic basal cell carcinoma) had received study drug and had the potential to be followed up for 12 months or longer. Treatment was discontinued in 400 (80%) patients; 180 (36%) had adverse events, 70 (14%) had progressive disease, and 51 (10%) requested to stop treatment. Median duration of vismodegib exposure was 36·4 weeks (IQR 17·7-62·0). Adverse events happened in 491 (98%) patients; the most common were muscle spasms (317 [64%]), alopecia (307 [62%]), dysgeusia (269 [54%]), weight loss (162 [33%]), asthenia (141 [28%]), decreased appetite (126 [25%]), ageusia (112 [22%]), diarrhoea (83 [17%]), nausea (80 [16%]), and fatigue (80 [16%]). Most adverse events were grade 1 or 2. We recorded serious adverse events in 108 (22%) of 499 patients. Of the 31 patients who died, 21 were the result of adverse events. As assessed by investigators, 302 (66·7%, 62·1-71·0) of 453 patients with locally advanced basal cell carcinoma had an overall response (153 complete responses and 149 partial responses); 11 (37·9%; 20·7-57·7) of 29 patients with metastatic basal cell carcinoma had an overall response (two complete responses, nine partial responses). This study assessed the use of vismodegib in a setting representative of routine clinical practice for patients with advanced basal cell carcinoma. Our results show that treatment with vismodegib adds a novel therapeutic modality from which patients with advanced basal cell carcinoma can benefit substantially. F Hoffmann-La Roche. Copyright © 2015 Elsevier Ltd. All rights reserved.

Thermal history regulates methylbutenol basal emission rate in Pinus ponderosa.

PubMed

Gray, Dennis W; Goldstein, Allen H; Lerdau, Manuel T

2006-07-01

Methylbutenol (MBO) is a 5-carbon alcohol that is emitted by many pines in western North America, which may have important impacts on the tropospheric chemistry of this region. In this study, we document seasonal changes in basal MBO emission rates and test several models predicting these changes based on thermal history. These models represent extensions of the ISO G93 model that add a correction factor C(basal), allowing MBO basal emission rates to change as a function of thermal history. These models also allow the calculation of a new emission parameter E(standard30), which represents the inherent capacity of a plant to produce MBO, independent of current or past environmental conditions. Most single-component models exhibited large departures in early and late season, and predicted day-to-day changes in basal emission rate with temporal offsets of up to 3 d relative to measured basal emission rates. Adding a second variable describing thermal history at a longer time scale improved early and late season model performance while retaining the day-to-day performance of the parent single-component model. Out of the models tested, the T(amb),T(max7) model exhibited the best combination of day-to-day and seasonal predictions of basal MBO emission rates.

Observation of a unique case of metastatic basal cell carcinoma found by radiographic evaluation in a patient with oculocutaneous albinism

PubMed Central

Johnston, Mickaila

2014-01-01

Background: Basal cell carcinoma is one of the more common cancers worldwide; 2.8 million are diagnosed annually in the USA.  However, the rate at which it metastasizes is considered very low, between 0.0028 and 0.5%.  For those rare cases in which metastases occur, approximately one third metastasize to the lung.  Case: Presented is a 62-year-old Caucasian male with oculocutaneous albinism and a history of basal cell carcinomas occurring in multiple anatomic sites, most recently at the bilateral forearm and back.  Surveillance PET/CT imaging led to the discovery of no less than 30 lung nodules which were consistent with basal cell carcinoma on biopsy.  Histological features were remarkably similar in both the primary tumor and in the metastases. Conclusion:  An unusual case of a non-head and neck primary basal cell carcinoma metastatic to the lung was discovered on surveillance PET/CT imaging, in a patient with oculocutaneous albinism. PMID:24555117

Evaluation of surgical margins according to the histological type of basal cell carcinoma.

PubMed

Godoy, Charles Antonio Pires de; Neta, Alice Lima de Oliveira; Leão, Sofia Silveira de Souza; Dantas, Raul Lima; Carvalho, Valeska Oliveira Fonseca; Silva, Samuel Freire da

2017-01-01

Basal cell carcinoma is the most common skin cancer in the world. The aim of this study was to evaluate the surgical margin of basal cell carcinoma and correlate this with its histologic subtype. A retrospective analysis of pathology laboratory records from 1990 to 2000 was performed and the following data was collected: age, sex, race, anatomical location, histological type, and state of the excision margins in 1,428 histopathological reports of basal cell carcinoma. Ages ranged from 6 to 99 years, with an average of 57. There was a slight predominance of lesions in white women patients, and the most common histological subtype was the nodular, followed by the superficial. The most common locations were in the head and neck, with highest prevalence appeared in the nose. Surgical margins revealed a lateral involvement of 20.14% and a deep involvement of 12.47%. The fibrosing basal cell carcinoma is the histological type that most often presented positive surgical margins.

Giant basal cell carcinoma of the face: surgical management and challenges for reconstruction.

PubMed

Maimaiti, A; Mijiti, A; Yarbag, A; Moming, A

2016-02-01

Giant basal cell carcinoma, in which the tumour measures 5 cm or greater in diameter, is a very rare skin malignancy that accounts for less than 1 per cent of all basal cell tumours. Very few studies have reported on the incidence, resection and reconstruction of this lesion worldwide. In total, 17 patients with giant basal cell carcinoma of the head and neck region underwent surgical excision and reconstruction at our hospital. Medical charts were retrospectively reviewed and analysed. The lesion was usually in the forehead, eyelid, lips or nasal-cheek region. The greatest diameter ranged from 5 to 11 cm, with 5-6 cm being the most common size at the time of presentation. All patients had their tumour resected and reconstructed in a single-stage procedure, mostly with a local advancement flap, and with no post-operative flap failure. Giant basal cell carcinoma of the head and neck can be successfully treated with a local flap in a single-stage approach.

Expression of Ulex europaeus agglutinin I lectin-binding sites in squamous cell carcinomas and their absence in basal cell carcinomas. Indicator of tumor type and differentiation.

PubMed

Heng, M C; Fallon-Friedlander, S; Bennett, R

1992-06-01

Lectins bind tightly to carbohydrate moieties on cell surfaces. Alterations in lectin binding have been reported to accompany epidermal cell differentiation, marking alterations in membrane sugars during this process. The presence of UEA I (Ulex europaeus agglutinin I) L-fucose-specific lectin-binding sites has been used as a marker for terminally differentiated (committed) keratinocytes. In this article, we report the presence of UEA-I-binding sites on squamous keratinocytes of well-differentiated squamous cell carcinomas, with patchy loss of UEA I positivity on poorly differentiated cells of squamous cell carcinomas, suggesting a possible use for this technique in the rapid assessment of less differentiated areas within the squamous cell tumor. The absence of UEA-I-binding sites on basal cell carcinomas may be related to an inability of cells comprising this tumor to convert the L-D-pyranosyl moiety on basal cells to the L-fucose moiety, resulting in an inability of basal cell carcinoma cell to undergo terminal differentiation into a committed keratinocyte.

Management of Mucosal Basal Cell Carcinoma of the Lip: An Update and Comprehensive Review of the Literature.

PubMed

Loh, Tiffany; Rubin, Ashley G; Brian Jiang, Shang I

2016-12-01

Basal cell carcinoma (BCC) is the most common malignancy in the United States. Most BCCs occur on cutaneous surfaces, but rare cases on the mucosal lip have also been documented. Because only a small number of mucosal BCC (mBCC) cases have been reported, data on their clinical characteristics and management are limited. To perform an updated literature review of the management of mBCCs on the lip. A comprehensive literature review was conducted through a search of the PubMed database with the key phrases "mucosal basal cell carcinoma," "basal cell carcinoma mucosa," and "basal cell carcinoma lip mucosa." Forty-eight cases of mBCCs have been reported, and 35 had sufficient data for analysis. The average age at presentation was 66.8 years, and 57% (n = 20) had a history of skin cancer. Most cases were treated with surgical excision or Mohs micrographic surgery (MMS), with only 1 recurrence in the literature. Furthermore, the authors present 8 additional cases of mBCCs successfully treated with MMS. Mucosal basal cell carcinomas are rare, and skin cancer history may be a risk factor. Because the lip is a cosmetically and functionally important area, MMS may be the preferred treatment method for mBCCs in this location.

Basal Cell Carcinoma of the Dorsal Foot: An Update and Comprehensive Review of the Literature.

PubMed

Loh, Tiffany Y; Rubin, Ashley G; Jiang, Shang I Brian

2017-01-01

Ultraviolet radiation is a well-known risk factor for basal cell carcinoma (BCC). Therefore, the high incidence of BCCs in sun-exposed areas such as the head and neck is unsurprising. However, unexpectedly, BCCs on the sun-protected dorsal foot have also been reported, and tumor occurrence here suggests that other factors besides ultraviolet radiation may play a role in BCC pathogenesis. Because only few dorsal foot BCCs have been reported, data on their clinical features and management are limited. To perform an updated review of the literature on clinical characteristics and treatment of dorsal foot BCCs. We conducted a comprehensive literature review by searching the PubMed database with the key phrases "basal cell carcinoma dorsal foot," "basal cell carcinoma foot," and "basal cell carcinoma toe." We identified 20 cases of dorsal foot BCCs in the literature, 17 of which had sufficient data for analysis. Only 1 case was treated with Mohs micrographic surgery. We present 8 additional cases of dorsal foot BCCs treated with Mohs micrographic surgery. Basal cell carcinomas on the dorsal foot are rare, and potential risk factors include Caucasian descent and personal history of skin cancer. Mohs micrographic surgery seems to be an effective treatment option.

Red Dot Basal Cell Carcinoma: An Unusual Variant of a Common Malignancy.

PubMed

Loh, Tiffany Y; Cohen, Philip R

2016-05-01

Red dot basal cell carcinoma is a distinct but rare subtype of basal cell carcinoma (BCC). It presents as a red macule or papule; therefore, in most cases, it may easily be mistaken for a benign vascular lesion, such as a telangiectasia or angioma.
A red dot BCC in an older woman is described. Clinical and histological differences between red dot BCCs and telangiectasias are described.
A 72-year-old woman initially presented with a painless red macule on her nose. Biopsy of the lesion established the diagnosis of a red dot BCC. Pubmed was searched for the following terms: angioma, basal cell carcinoma, dermoscope, diascopy, red dot, non-melanoma skin cancer, telangiectasia, and vascular. The papers were reviewed for cases of red dot basal cell carcinoma. Clinical and histological characteristics of red dot basal cell carcinoma and telangiectasias were compared.
Red dot BCC is an extremely rare variant of BCC that may be confused with benign vascular lesions. Although BCCs rarely metastasize and are associated with low mortality, they have the potential to become locally invasive and destructive if left untreated. Thus, a high index of suspicion for red dot BCC is necessary.

J Drugs Dermatol. 2016;15(5):645-647.

Two cases of seborrheic keratosis with basal clear cells.

PubMed

Anan, Takashi; Fukumoto, Takaya; Kimura, Tetsunori

2017-03-01

Seborrheic keratosis with basal clear cells (SKBCC) is an extremely rare histopathological variant of seborrheic keratosis that has histological similarities to melanoma in situ. We herein report two cases of SKBCC and provide the first description of the dermoscopic features of this condition, in addition to the histopathological findings. Both of the two lesions showed typical histological architectures of seborrheic keratosis with rows or focal clusters of monomorphic clear cells with abundant pale cytoplasm and small round nucleus in the basal layer. Immunohistochemical examination revealed that most clear cells were positive for high molecular weight cytokeratin (34βE12) in a peripheral pattern but were negative tor Melan-A. Dermoscopy revealed typical features of ordinary seborrheic keratosis, while unfortunately did not reflect the presence of basal clear cells. © 2016 Japanese Dermatological Association.

Genetics and risk factors for basal cell carcinoma.

PubMed

Madan, V; Hoban, P; Strange, R C; Fryer, A A; Lear, J T

2006-05-01

Nonmelanoma skin cancer (NMSC) is the commonest cancer in whites and its incidence is increasing worldwide. The prevalence of this cancer is predicted to equal that of all others combined and it was estimated that there were over 2 million cases diagnosed in the U.S.A. in 2004. Patients exhibit marked differences in clinical phenotype with variations in tumour numbers, rate of tumour accrual, site and histological subtype. Furthermore, patients are at increased risk of other cutaneous and noncutaneous cancers. The factors accounting for this variation are complex and still not completely understood. Clearly, ultraviolet light (UV) exposure is a major influence but its relationship to clinical phenotype is not yet clear. In addition, immunosuppression is a significant risk factor. Our group has identified high-risk groups for the development of further basal cell carcinoma (BCC), namely patients with truncal BCC and those presenting with tumour clusters. This presentation will concentrate on these clinical subgroups as well as immunosuppressed patients. These groups represent significant management challenges and are areas where novel, nonsurgical treatment options may make a significant clinical impact in patient care. The risk factors predisposing to these clinical phenotypes will be discussed, including genetic factors and UV exposure. Potential clinical applications, including predictive indices, will be considered.

A time- and matrix-dependent TGFBR3–JUND–KRT5 regulatory circuit in single breast epithelial cells and basal-like premalignancies

PubMed Central

Wang, Chun-Chao; Bajikar, Sameer S.; Jamal, Leen; Atkins, Kristen A.; Janes, Kevin A.

2014-01-01

Basal-like breast carcinoma is characterized by poor prognosis and high intratumor heterogeneity. In an immortalized basal-like breast epithelial cell line, we identified two anti-correlated gene-expression programs that arise among single extracellular matrix (ECM)-attached cells during organotypic 3D culture. The first contains multiple TGFβ-related genes including TGFBR3, whereas the second contains JUND and the basal-like marker, KRT5. TGFBR3 and JUND interconnect through four negative-feedback loops to form a circuit that exhibits spontaneous damped oscillations in 3D culture. The TGFBR3–JUND circuit appears conserved in some premalignant lesions that heterogeneously express KRT5. The circuit depends on ECM engagement, as detachment causes a rewiring that is triggered by RPS6 dephosphorylation and maintained by juxtacrine tenascin C, which is critical for intraductal colonization of basal-like breast cancer cells in vivo. Intratumor heterogeneity need not stem from partial differentiation and could instead reflect dynamic toggling of cells between expression states that are not cell autonomous. PMID:24658685

Chemoprevention of Basal and Squamous Cell Carcinoma With a Single Course of Fluorouracil, 5%, Cream: A Randomized Clinical Trial.

PubMed

Weinstock, Martin A; Thwin, Soe Soe; Siegel, Julia A; Marcolivio, Kimberly; Means, Alexander D; Leader, Nicholas F; Shaw, Fiona M; Hogan, Daniel; Eilers, David; Swetter, Susan M; Chen, Suephy C; Jacob, Sharon E; Warshaw, Erin M; Stricklin, George P; Dellavalle, Robert P; Sidhu-Malik, Navjeet; Konnikov, Nellie; Werth, Victoria P; Keri, Jonette E; Robinson-Bostom, Leslie; Ringer, Robert J; Lew, Robert A; Ferguson, Ryan; DiGiovanna, John J; Huang, Grant D

2018-02-01

Keratinocyte carcinoma (ie, cutaneous basal and squamous cell carcinoma) is the most common cancer in the United States. To determine whether topical fluorouracil could prevent surgically treated keratinocyte carcinoma. The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized, double-blind, placebo-controlled trial of topical fluorouracil for chemoprevention of keratinocyte carcinoma. Participants were recruited from May 2009 to September 2011 from 12 Veterans Affairs medical centers and followed until June 30, 2013. Participants were veterans (n = 932) with a history of at least 2 keratinocyte carcinomas in the past 5 years; almost all were white males and the median age was 70 years. Application of fluorouracil, 5%, (n = 468) or vehicle control cream (n = 464) to the face and ears twice daily for 2 to 4 weeks upon randomization. Surgically treated keratinocyte, basal cell, and squamous cell carcinoma risk on the face and ears in the first year after enrollment; and time to first surgically treated keratinocyte, basal cell, and squamous cell carcinoma. The a priori hypothesis was that fluorouracil would be effective in preventing these cancers. Of 932 participants (916 men [98%]; 926 white [99%]; median age, 70 years), 299 developed a basal cell carcinoma end point (95 in year 1) and 108 developed a squamous cell carcinoma end point (25 in year 1) over 4 years (median follow-up, 2.8 years). Over the entire study, there was no difference between treatment groups in time to first keratinocyte, basal cell, or squamous cell carcinoma. During the first year, however, 5 participants (1%) in the fluorouracil group developed a squamous cell carcinoma vs 20 (4%) in the control group, a 75% (95% CI, 35%-91%) risk reduction (P = .002). The 11% reduction in basal cell carcinoma risk during year 1 (45 [10%] in the fluorouracil group vs 50 [11%] in the control group) was not statistically significant (95% CI, 39% reduction to 31% increase), nor was there a significant effect on keratinocyte carcinoma risk. However, a reduction in keratinocyte carcinomas treated with Mohs surgery was observed. A conventional course of fluorouracil to the face and ears substantially reduces surgery for squamous cell carcinoma for 1 year without significantly affecting the corresponding risk for basal cell carcinoma. clinicaltrials.gov Identifier: NCT00847912.

Role of HGF in epithelial–stromal cell interactions during progression from benign breast disease to ductal carcinoma in situ

PubMed Central

2013-01-01

Introduction Basal-like and luminal breast cancers have distinct stromal–epithelial interactions, which play a role in progression to invasive cancer. However, little is known about how stromal–epithelial interactions evolve in benign and pre-invasive lesions. Methods To study epithelial–stromal interactions in basal-like breast cancer progression, we cocultured reduction mammoplasty fibroblasts with the isogenic MCF10 series of cell lines (representing benign/normal, atypical hyperplasia, and ductal carcinoma in situ). We used gene expression microarrays to identify pathways induced by coculture in premalignant cells (MCF10DCIS) compared with normal and benign cells (MCF10A and MCF10AT1). Relevant pathways were then evaluated in vivo for associations with basal-like subtype and were targeted in vitro to evaluate effects on morphogenesis. Results Our results show that premalignant MCF10DCIS cells express characteristic gene expression patterns of invasive basal-like microenvironments. Furthermore, while hepatocyte growth factor (HGF) secretion is upregulated (relative to normal, MCF10A levels) when fibroblasts are cocultured with either atypical (MCF10AT1) or premalignant (MCF10DCIS) cells, only MCF10DCIS cells upregulated the HGF receptor MET. In three-dimensional cultures, upregulation of HGF/MET in MCF10DCIS cells induced morphological changes suggestive of invasive potential, and these changes were reversed by antibody-based blocking of HGF signaling. These results are relevant to in vivo progression because high expression of a novel MCF10DCIS-derived HGF signature was correlated with the basal-like subtype, with approximately 86% of basal-like cancers highly expressing the HGF signature, and because high expression of HGF signature was associated with poor survival. Conclusions Coordinated and complementary changes in HGF/MET expression occur in epithelium and stroma during progression of pre-invasive basal-like lesions. These results suggest that targeting stroma-derived HGF signaling in early carcinogenesis may block progression of basal-like precursor lesions. PMID:24025166

Molecular subtype-specific immunocompetent models of high-grade urothelial carcinoma reveal differential neoantigen expression and response to immunotherapy.

PubMed

Saito, Ryoichi; Smith, Christof C; Utsumi, Takanobu; Bixby, Lisa M; Kardos, Jordan; Wobker, Sara E; Stewart, Kyle G; Chai, Shengjie; Manocha, Ujjawal; Byrd, Kevin Matthew; Damrauer, Jeffrey S; Williams, Scott E; Vincent, Benjamin G; Kim, William Y

2018-05-21

High-grade urothelial cancer contains intrinsic molecular subtypes that exhibit differences in underlying tumor biology and can be divided into luminal-like and basal-like subtypes. We describe here the first subtype-specific murine models of bladder cancer and show that Upk3a-CreERT2; Trp53L/L; PtenL/L; Rosa26LSL-Luc (UPPL: luminal-like) and BBN (basal-like) tumors are more faithful to human bladder cancer than the widely-used MB49 cells. Following engraftment into immunocompetent C57BL/6 mice, BBN tumors were more responsive to PD-1 inhibition than UPPL tumors. Responding tumors within the BBN model showed differences in immune microenvironment composition, including increased ratios of CD8+:CD4+ and memory:regulatory T cells. Finally, we predicted and confirmed immunogenicity of tumor neoantigens in each model. These UPPL and BBN models will be a valuable resource for future studies examining bladder cancer biology and immunotherapy. Copyright ©2018, American Association for Cancer Research.

Cytokeratin characterization of human prostatic carcinoma and its derived cell lines.

PubMed

Nagle, R B; Ahmann, F R; McDaniel, K M; Paquin, M L; Clark, V A; Celniker, A

1987-01-01

Two murine monoclonal anti-cytokeratin antibodies with defined specificity were shown to distinguish between basal cells and luminal cells in human prostate tissue. Forty-one biopsies or transurethral resection specimens were characterized using these two antibodies. In cases of benign prostatic hyperplasia, focal loss of the basal cell layer was noted in areas of glandular proliferation. Ten cases of adenocarcinoma of the prostate, varying in Gleason's histological grade from 2 to 4, were also studied. In each case the carcinoma was shown to represent the luminal cell phenotype with no evidence of involvement of the basal cell phenotype. An analysis of three established metastatic prostatic carcinoma cell lines (DU-145, PC-3, and LNCaP) using two-dimensional electrophoresis showed that the cytokeratin complement of each cell line was slightly different but retained the phenotype of the luminal cell. It was concluded that during both hyperplasia and neoplastic transformation of the prostate, the luminal cell phenotype is primarily involved and that the basal cell phenotype does not appear to contribute to either intraluminal proliferation or invasive cell populations.

Ablation of cdk4 and cdk6 affects proliferation of basal progenitor cells in the developing dorsal and ventral forebrain.

PubMed

Grison, Alice; Gaiser, Carine; Bieder, Andrea; Baranek, Constanze; Atanasoski, Suzana

2018-03-23

Little is known about the molecular players driving proliferation of neural progenitor cells (NPCs) during embryonic mouse development. Here, we demonstrate that proliferation of NPCs in the developing forebrain depends on a particular combination of cell cycle regulators. We have analyzed the requirements for members of the cyclin-dependent kinase (cdk) family using cdk-deficient mice. In the absence of either cdk4 or cdk6, which are both regulators of the G1 phase of the cell cycle, we found no significant effects on the proliferation rate of cortical progenitor cells. However, concomitant loss of cdk4 and cdk6 led to a drastic decrease in the proliferation rate of NPCs, specifically the basal progenitor cells of both the dorsal and ventral forebrain at embryonic day 13.5 (E13.5). Moreover, basal progenitors in the forebrain of Cdk4;Cdk6 double mutant mice exhibited altered cell cycle characteristics. Cdk4;cdk6 deficiency led to an increase in cell cycle length and cell cycle exit of mutant basal progenitor cells in comparison to controls. In contrast, concomitant ablation of cdk2 and cdk6 had no effect on the proliferation of NCPs. Together, our data demonstrate that the expansion of the basal progenitor pool in the developing telencephalon is dependent on the presence of distinct combinations of cdk molecules. Our results provide further evidence for differences in the regulation of proliferation between apical and basal progenitors during cortical development. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018. © 2018 Wiley Periodicals, Inc.

The terminal basal mitosis of chicken retinal Lim1 horizontal cells is not sensitive to cisplatin-induced cell cycle arrest.

PubMed

Shirazi Fard, Shahrzad; Thyselius, Malin; All-Ericsson, Charlotta; Hallböök, Finn

2014-01-01

For proper development, cells need to coordinate proliferation and cell cycle-exit. This is mediated by a cascade of proteins making sure that each phase of the cell cycle is controlled before the initiation of the next. Retinal progenitor cells divide during the process of interkinetic nuclear migration, where they undergo S-phase on the basal side, followed by mitoses on the apical side of the neuroepithelium. The final cell cycle of chicken retinal horizontal cells (HCs) is an exception to this general cell cycle behavior. Lim1 expressing (+) horizontal progenitor cells (HPCs) have a heterogenic final cell cycle, with some cells undergoing a terminal mitosis on the basal side of the retina. The results in this study show that this terminal basal mitosis of Lim1+ HPCs is not dependent on Chk1/2 for its regulation compared to retinal cells undergoing interkinetic nuclear migration. Neither activating nor blocking Chk1 had an effect on the basal mitosis of Lim1+ HPCs. Furthermore, the Lim1+ HPCs were not sensitive to cisplatin-induced DNA damage and were able to continue into mitosis in the presence of γ-H2AX without activation of caspase-3. However, Nutlin3a-induced expression of p21 did reduce the mitoses, suggesting the presence of a functional p53/p21 response in HPCs. In contrast, the apical mitoses were blocked upon activation of either Chk1/2 or p21, indicating the importance of these proteins during the process of interkinetic nuclear migration. Inhibiting Cdk1 blocked M-phase transition both for apical and basal mitoses. This confirmed that the cyclin B1-Cdk1 complex was active and functional during the basal mitosis of Lim1+ HPCs. The regulation of the final cell cycle of Lim1+ HPCs is of particular interest since it has been shown that the HCs are able to sustain persistent DNA damage, remain in the cell cycle for an extended period of time and, consequently, survive for months.

Repair of tracheal epithelium by basal cells after chlorine-induced injury

PubMed Central

2012-01-01

Background Chlorine is a widely used toxic compound that is considered a chemical threat agent. Chlorine inhalation injures airway epithelial cells, leading to pulmonary abnormalities. Efficient repair of injured epithelium is necessary to restore normal lung structure and function. The objective of the current study was to characterize repair of the tracheal epithelium after acute chlorine injury. Methods C57BL/6 mice were exposed to chlorine and injected with 5-ethynyl-2′-deoxyuridine (EdU) to label proliferating cells prior to sacrifice and collection of tracheas on days 2, 4, 7, and 10 after exposure. Airway repair and restoration of a differentiated epithelium were examined by co-localization of EdU labeling with markers for the three major tracheal epithelial cell types [keratin 5 (K5) and keratin 14 (K14) for basal cells, Clara cell secretory protein (CCSP) for Clara cells, and acetylated tubulin (AcTub) for ciliated cells]. Morphometric analysis was used to measure proliferation and restoration of a pseudostratified epithelium. Results Epithelial repair was fastest and most extensive in proximal trachea compared with middle and distal trachea. In unexposed mice, cell proliferation was minimal, all basal cells expressed K5, and K14-expressing basal cells were absent from most sections. Chlorine exposure resulted in the sloughing of Clara and ciliated cells from the tracheal epithelium. Two to four days after chlorine exposure, cell proliferation occurred in K5- and K14-expressing basal cells, and the number of K14 cells was dramatically increased. In the period of peak cell proliferation, few if any ciliated or Clara cells were detected in repairing trachea. Expression of ciliated and Clara cell markers was detected at later times (days 7–10), but cell proliferation was not detected in areas in which these differentiated markers were re-expressed. Fibrotic lesions were observed at days 7–10 primarily in distal trachea. Conclusion The data are consistent with a model where surviving basal cells function as progenitor cells to repopulate the tracheal epithelium after chlorine injury. In areas with few remaining basal cells, repair is inefficient, leading to airway fibrosis. These studies establish a model for understanding regenerative processes in the respiratory epithelium useful for testing therapies for airway injury. PMID:23170909

Sonic hedgehog-expressing basal cells are general post-mitotic precursors of functional taste receptor cells

PubMed Central

Miura, Hirohito; Scott, Jennifer K.; Harada, Shuitsu; Barlow, Linda A.

2014-01-01

Background Taste buds contain ~60 elongate cells and several basal cells. Elongate cells comprise three functional taste cell types: I - glial cells, II - bitter/sweet/umami receptor cells, and III - sour detectors. Although taste cells are continuously renewed, lineage relationships among cell types are ill-defined. Basal cells have been proposed as taste bud stem cells, a subset of which express Sonic hedgehog (Shh). However, Shh+ basal cells turnover rapidly suggesting that Shh+ cells are precursors of some or all taste cell types. Results To fate map Shh-expressing cells, mice carrying ShhCreERT2 and a high (CAG-CAT-EGFP) or low (R26RLacZ) efficiency reporter allele were given tamoxifen to activate Cre in Shh+ cells. Using R26RLacZ, lineage-labeled cells occur singly within buds, supporting a post-mitotic state for Shh+ cells. Using either reporter, we show that Shh+ cells differentiate into all three taste cell types, in proportions reflecting cell type ratios in taste buds (I > II > III). Conclusions Shh+ cells are not stem cells, but are post-mitotic, immediate precursors of taste cells. Shh+ cells differentiate into each of the three taste cell types, and the choice of a specific taste cell fate is regulated to maintain the proper ratio within buds. PMID:24590958

Training a cell-level classifier for detecting basal-cell carcinoma by combining human visual attention maps with low-level handcrafted features

PubMed Central

Corredor, Germán; Whitney, Jon; Arias, Viviana; Madabhushi, Anant; Romero, Eduardo

2017-01-01

Abstract. Computational histomorphometric approaches typically use low-level image features for building machine learning classifiers. However, these approaches usually ignore high-level expert knowledge. A computational model (M_im) combines low-, mid-, and high-level image information to predict the likelihood of cancer in whole slide images. Handcrafted low- and mid-level features are computed from area, color, and spatial nuclei distributions. High-level information is implicitly captured from the recorded navigations of pathologists while exploring whole slide images during diagnostic tasks. This model was validated by predicting the presence of cancer in a set of unseen fields of view. The available database was composed of 24 cases of basal-cell carcinoma, from which 17 served to estimate the model parameters and the remaining 7 comprised the evaluation set. A total of 274 fields of view of size 1024×1024  pixels were extracted from the evaluation set. Then 176 patches from this set were used to train a support vector machine classifier to predict the presence of cancer on a patch-by-patch basis while the remaining 98 image patches were used for independent testing, ensuring that the training and test sets do not comprise patches from the same patient. A baseline model (M_ex) estimated the cancer likelihood for each of the image patches. M_ex uses the same visual features as M_im, but its weights are estimated from nuclei manually labeled as cancerous or noncancerous by a pathologist. M_im achieved an accuracy of 74.49% and an F-measure of 80.31%, while M_ex yielded corresponding accuracy and F-measures of 73.47% and 77.97%, respectively. PMID:28382314

The detection of basal cell determinants in human basal cell carcinomas using two different monoclonal antibodies.

PubMed

Habets, J M; Tank, B; Vuzevski, V D; van Reede, E C; Stolz, E; van Joost, T

1987-01-01

This report deals with the reaction pattern(s) of two monoclonal antibodies (MoAbs) with normal skin and basal cell carcinomas (BCC). Using indirect immunoperoxidase (IIP) and indirect immunofluorescence (IIF) techniques, MoAb 12 G7 was observed to react with a determinant related to the cell membrane of the epidermal basal cells. In the IIP technique MoAb 12 G7 showed a positive reaction with 32 out of 34 BCC (94%), while in IIF all the 14 BCC that were studied were positive. In most cases only the cells at the periphery of the tumour nests were stained. MoAb 253 B7 reacted with cytoplasmic determinant(s) of the epidermal basal cells both in the IIF as well as in the IIP techniques. Using the IIP technique only 5 out of 34 BCC (15%) showed a positive reaction with this MoAb. Four of the 5 positively staining tumours showed aggressive histological features. Using IIF technique only 2 out of 14 BCC were positive. The results presented in this communication are discussed with regard to the possible expression of selective differentiation and tumor-associated determinant(s) in BCC.

Basal cell carcinoma, squamous cell carcinoma and melanoma of the head and face.

PubMed

Feller, L; Khammissa, R A G; Kramer, B; Altini, M; Lemmer, J

2016-02-05

Ultraviolet light (UV) is an important risk factor for cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin. These cancers most commonly affect persons with fair skin and blue eyes who sunburn rather than suntan. However, each of these cancers appears to be associated with a different pattern of UV exposure and to be mediated by different intracellular molecular pathways.Some melanocortin 1 receptor (MC1R) gene variants play a direct role in the pathogenesis of cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma apart from their role in determining a cancer-prone pigmentory phenotype (fair skin, red hair, blue eyes) through their interactions with other genes regulating immuno-inflammatory responses, DNA repair or apoptosis.In this short review we focus on the aetiological role of UV in cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin, and on some associated biopathological events.

The core planar cell polarity gene, Vangl2, maintains apical-basal organisation of the corneal epithelium.

PubMed

Panzica, D Alessio; Findlay, Amy S; van Ladesteijn, Rianne; Collinson, J Martin

2017-08-17

The role of the core planar cell polarity (PCP) pathway protein, Vangl2, was investigated in the corneal epithelium of the mammalian eye, a paradigm anatomical model of planar cell migration. The gene was conditionally knocked out in vivo and knocked down by siRNA, followed by immunohistochemical, behavioural and morphological analysis of corneal epithelial cells. The primary defects observed in vivo were of apical-basal organisation of the corneal epithelium, with abnormal stratification throughout life, mislocalisation of the cell membrane protein, Scribble, to the basal side of cells, and partial loss of the epithelial basement membrane. Planar defects in migration after wounding and in the presence of an applied electric field were noted. However, knockdown of Vangl2 also retarded cell migration in individual cells that had no contact with their neighbours, which precluded a classic PCP mechanism. It is concluded that some of the planar polarity phenotypes in PCP mutants may arise from disruption of apical-basal polarity. © 2017 Anatomical Society.

Non-canonical features of the Golgi apparatus in bipolar epithelial neural stem cells

PubMed Central

Taverna, Elena; Mora-Bermúdez, Felipe; Strzyz, Paulina J.; Florio, Marta; Icha, Jaroslav; Haffner, Christiane; Norden, Caren; Wilsch-Bräuninger, Michaela; Huttner, Wieland B.

2016-01-01

Apical radial glia (aRG), the stem cells in developing neocortex, are unique bipolar epithelial cells, extending an apical process to the ventricle and a basal process to the basal lamina. Here, we report novel features of the Golgi apparatus, a central organelle for cell polarity, in mouse aRGs. The Golgi was confined to the apical process but not associated with apical centrosome(s). In contrast, in aRG-derived, delaminating basal progenitors that lose apical polarity, the Golgi became pericentrosomal. The aRG Golgi underwent evolutionarily conserved, accordion-like compression and extension concomitant with cell cycle-dependent nuclear migration. Importantly, in line with endoplasmic reticulum but not Golgi being present in the aRG basal process, its plasma membrane contained glycans lacking Golgi processing, consistent with direct ER-to-cell surface membrane traffic. Our study reveals hitherto unknown complexity of neural stem cell polarity, differential Golgi contribution to their specific architecture, and fundamental Golgi re-organization upon cell fate change. PMID:26879757

Three cell recognition changes accompany the ingression of sea urchin primary mesenchyme cells.

PubMed

Fink, R D; McClay, D R

1985-01-01

At gastrulation the primary mesenchyme cells of sea urchin embryos lose contact with the extracellular hyaline layer and with neighboring blastomeres as they pass through the basal lamina and enter the blastocoel. This delamination process was examined using a cell-binding assay to follow changes in affinities between mesenchyme cells and their three substrates: hyalin, early gastrula cells, and basal lamina. Sixteen-cell-stage micromeres (the precursors of primary mesenchyme cells), and mesenchyme cells obtained from mesenchyme-blastula-stage embryos were used in conjunction with micromeres raised in culture to intermediate ages. The micromeres exhibited an affinity for hyalin, but the affinity was lost at the time of mesenchyme ingression in vivo. Similarly, micromeres had an affinity for monolayers of gastrula cells but the older mesenchyme cells lost much of their cell-to-cell affinity. Presumptive ectoderm and endoderm cells tested against the gastrula monolayers showed no decrease in binding over the same time interval. When micromeres and primary mesenchyme cells were tested against basal lamina preparations, there was an increase in affinity that was associated with developmental time. Presumptive ectoderm and endoderm cells showed no change in affinity over the same interval. Binding measurements using isolated basal laminar components identified fibronectin as one molecule for which the wandering primary mesenchyme cells acquired a specific affinity. The data indicate that as the presumptive mesenchyme cells leave the vegetal plate of the embryo they lose affinities for hyalin and for neighboring cells, and gain an affinity for fibronectin associated with the basal lamina and extracellular matrix that lines the blastocoel.

Accelerated cell-sheet recovery from a surface successively grafted with polyacrylamide and poly(N-isopropylacrylamide).

PubMed

Akiyama, Yoshikatsu; Kikuchi, Akihiko; Yamato, Masayuki; Okano, Teruo

2014-08-01

A double polymeric nanolayer consisting of poly(N-isopropylacrylamide) (PIPAAm) and hydrophilic polyacrylamide (PAAm) was deposited on tissue culture polystyrene (TCPS) surfaces using electron beam irradiation to form a new temperature-responsive cell culture surface in which the basal hydrophilic PAAm component in the double polymeric layer promotes the hydration of the upper PIPAAm layer and induces rapid cell detachment compared to a conventional temperature-responsive cell culture surface, PIPAAm-grafted TCPS (PIPAAm-TCPS). Take-off angle-dependent X-ray photoelectron spectroscopy spectral analysis demonstrated that the grafted PIPAAm and PAAm components were located in the upper and basal regions of the double polymeric layer, respectively, suggesting that the double polymeric layer forms an inter-penetrating-network-like structure with PAAm at the basal portion of the PIPAAm grafted chains. The wettability of the temperature-responsive cell culture surfaces with the double polymeric layer tended to be more hydrophilic, with an increase in the basal PAAm graft density at a constant PIPAAm graft density. However, when the graft densities of the upper PIPAAm and basal PAAm were optimized, the resulting temperature-responsive cell culture surface with the double polymeric layer exhibited rapid cell detachment while maintaining cell adhesive character comparable to that of PIPAAm-TCPS. The cell adhesive character was altered from cell-adhesive to cell-repellent with increasing PAAm or PIPAAm graft density. The cell adhesive character of the temperature-responsive cell culture surfaces was relatively consistent with their contact angles. These results strongly suggest that the basal PAAm surface properties affect the degree of hydration and dehydration of the subsequently grafted PIPAAm. In addition, the roles of the hydrophilic component in accelerating cell detachment are further discussed in terms of the mobility of the grafted PIPAAm chains. Applications of this insight might be useful for designing temperature-responsive cell culture surfaces for achieving efficient cell culture and quick target cell detachment. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

RNA Polymerase II cluster dynamics predict mRNA output in living cells

PubMed Central

Cho, Won-Ki; Jayanth, Namrata; English, Brian P; Inoue, Takuma; Andrews, J Owen; Conway, William; Grimm, Jonathan B; Spille, Jan-Hendrik; Lavis, Luke D; Lionnet, Timothée; Cisse, Ibrahim I

2016-01-01

Protein clustering is a hallmark of genome regulation in mammalian cells. However, the dynamic molecular processes involved make it difficult to correlate clustering with functional consequences in vivo. We developed a live-cell super-resolution approach to uncover the correlation between mRNA synthesis and the dynamics of RNA Polymerase II (Pol II) clusters at a gene locus. For endogenous β-actin genes in mouse embryonic fibroblasts, we observe that short-lived (~8 s) Pol II clusters correlate with basal mRNA output. During serum stimulation, a stereotyped increase in Pol II cluster lifetime correlates with a proportionate increase in the number of mRNAs synthesized. Our findings suggest that transient clustering of Pol II may constitute a pre-transcriptional regulatory event that predictably modulates nascent mRNA output. DOI: http://dx.doi.org/10.7554/eLife.13617.001 PMID:27138339

Transitional basal cells at the squamous-columnar junction generate Barrett’s oesophagus

PubMed Central

Jiang, Ming; Li, Haiyan; Zhang, Yongchun; Yang, Ying; Lu, Rong; Liu, Kuancan; Lin, Sijie; Lan, Xiaopeng; Wang, Haikun; Wu, Han; Zhu, Jian; Zhou, Zhongren; Xu, Jianming; Lee, Dong-Kee; Zhang, Lanjing; Lee, Yuan-Cho; Yuan, Jingsong; Abrams, Julian A.; Wang, Timothy G.; Sepulveda, Antonia R.; Wu, Qi; Chen, Huaiyong; Sun, Xin; She, Junjun; Chen, Xiaoxin; Que, Jianwen

2017-01-01

In several organ systems the transitional zone between different types of epithelia is a hotspot for pre-neoplastic metaplasia and malignancy1–3. However, the cell-of-origin for the metaplastic epithelium and subsequent malignancy, remains obscure1–3. In the case of Barrett’s oesophagus (BE), intestinal metaplasia occurs at the gastro-oesophageal junction, where stratified squamous epithelium transitions into simple columnar cells4. Based on different experimental models, several alternative cell types have been proposed as the source of the metaplasia, but in all cases the evidence is inconclusive and no model completely mimics BE with the presence of intestinal goblet cells5–8. Here, we describe a novel transitional columnar epithelium with distinct basal progenitor cells (p63+ KRT5+ KRT7+) in the squamous-columnar junction (SCJ) in the upper gastrointestinal tract of the mouse. We use multiple models and lineage tracing strategies to show that this unique SCJ basal cell population serves as a source of progenitors for the transitional epithelium. Moreover, upon ectopic expression of CDX2 these transitional basal progenitors differentiate into intestinal-like epithelium including goblet cells, thus reproducing Barrett’s metaplasia. A similar transitional columnar epithelium is present at the transitional zones of other mouse tissues, including the anorectal junction, and, importantly, at the gastro-oesophageal junction in the human gut. Acid reflux-induced oesophagitis and the multilayered epithelium (MLE) believed to be a precursor of BE are both characterized by the expansion of the transitional basal progenitor cells. Taken together our findings reveal the presence of a previously unidentified transitional zone in the epithelium of the upper gastrointestinal tract and provide evidence that the p63+ KRT7+ basal cells in this zone are the cell-of-origin for MLE and BE. PMID:29019984

Transitional basal cells at the squamous-columnar junction generate Barrett's oesophagus.

PubMed

Jiang, Ming; Li, Haiyan; Zhang, Yongchun; Yang, Ying; Lu, Rong; Liu, Kuancan; Lin, Sijie; Lan, Xiaopeng; Wang, Haikun; Wu, Han; Zhu, Jian; Zhou, Zhongren; Xu, Jianming; Lee, Dong-Kee; Zhang, Lanjing; Lee, Yuan-Cho; Yuan, Jingsong; Abrams, Julian A; Wang, Timothy C; Sepulveda, Antonia R; Wu, Qi; Chen, Huaiyong; Sun, Xin; She, Junjun; Chen, Xiaoxin; Que, Jianwen

2017-10-26

In several organ systems, the transitional zone between different types of epithelium is a hotspot for pre-neoplastic metaplasia and malignancy, but the cells of origin for these metaplastic epithelia and subsequent malignancies remain unknown. In the case of Barrett's oesophagus, intestinal metaplasia occurs at the gastro-oesophageal junction, where stratified squamous epithelium transitions into simple columnar cells. On the basis of a number of experimental models, several alternative cell types have been proposed as the source of this metaplasia but in all cases the evidence is inconclusive: no model completely mimics Barrett's oesophagus in terms of the presence of intestinal goblet cells. Here we describe a transitional columnar epithelium with distinct basal progenitor cells (p63 + KRT5 + KRT7 + ) at the squamous-columnar junction of the upper gastrointestinal tract in a mouse model. We use multiple models and lineage tracing strategies to show that this squamous-columnar junction basal cell population serves as a source of progenitors for the transitional epithelium. On ectopic expression of CDX2, these transitional basal progenitors differentiate into intestinal-like epithelium (including goblet cells) and thereby reproduce Barrett's metaplasia. A similar transitional columnar epithelium is present at the transitional zones of other mouse tissues (including the anorectal junction) as well as in the gastro-oesophageal junction in the human gut. Acid reflux-induced oesophagitis and the multilayered epithelium (believed to be a precursor of Barrett's oesophagus) are both characterized by the expansion of the transitional basal progenitor cells. Our findings reveal a previously unidentified transitional zone in the epithelium of the upper gastrointestinal tract and provide evidence that the p63 + KRT5 + KRT7 + basal cells in this zone are the cells of origin for multi-layered epithelium and Barrett's oesophagus.

Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival.

PubMed

Tiong, Kai Hung; Tan, Boon Shing; Choo, Heng Lungh; Chung, Felicia Fei-Lei; Hii, Ling-Wei; Tan, Si Hoey; Khor, Nelson Tze Woei; Wong, Shew Fung; See, Sze-Jia; Tan, Yuen-Fen; Rosli, Rozita; Cheong, Soon-Keng; Leong, Chee-Onn

2016-09-06

Basal-like breast cancer is an aggressive tumor subtype with poor prognosis. The discovery of underlying mechanisms mediating tumor cell survival, and the development of novel agents to target these pathways, is a priority for patients with basal-like breast cancer. From a functional screen to identify key drivers of basal-like breast cancer cell growth, we identified fibroblast growth factor receptor 4 (FGFR4) as a potential mediator of cell survival. We found that FGFR4 mediates cancer cell survival predominantly via activation of PI3K/AKT. Importantly, a subset of basal-like breast cancer cells also secrete fibroblast growth factor 19 (FGF19), a canonical ligand specific for FGFR4. siRNA-mediated silencing of FGF19 or neutralization of extracellular FGF19 by anti-FGF19 antibody (1A6) decreases AKT phosphorylation, suppresses cancer cell growth and enhances doxorubicin sensitivity only in the FGFR4+/FGF19+ breast cancer cells. Consistently, FGFR4/FGF19 co-expression was also observed in 82 out of 287 (28.6%) primary breast tumors, and their expression is strongly associated with AKT phosphorylation, Ki-67 staining, higher tumor stage and basal-like phenotype. In summary, our results demonstrated the presence of an FGFR4/FGF19 autocrine signaling that mediates the survival of a subset of basal-like breast cancer cells and suggest that inactivation of this autocrine loop may potentially serve as a novel therapeutic intervention for future treatment of breast cancers.

Glutamine Synthetase Is a Genetic Determinant of Cell Type–Specific Glutamine Independence in Breast Epithelia

PubMed Central

Kung, Hsiu-Ni; Marks, Jeffrey R.; Chi, Jen-Tsan

2011-01-01

Although significant variations in the metabolic profiles exist among different cells, little is understood in terms of genetic regulations of such cell type–specific metabolic phenotypes and nutrient requirements. While many cancer cells depend on exogenous glutamine for survival to justify the therapeutic targeting of glutamine metabolism, the mechanisms of glutamine dependence and likely response and resistance of such glutamine-targeting strategies among cancers are largely unknown. In this study, we have found a systematic variation in the glutamine dependence among breast tumor subtypes associated with mammary differentiation: basal- but not luminal-type breast cells are more glutamine-dependent and may be susceptible to glutamine-targeting therapeutics. Glutamine independence of luminal-type cells is associated mechanistically with lineage-specific expression of glutamine synthetase (GS). Luminal cells can also rescue basal cells in co-culture without glutamine, indicating a potential for glutamine symbiosis within breast ducts. The luminal-specific expression of GS is directly induced by GATA3 and represses glutaminase expression. Such distinct glutamine dependency and metabolic symbiosis is coupled with the acquisition of the GS and glutamine independence during the mammary differentiation program. Understanding the genetic circuitry governing distinct metabolic patterns is relevant to many symbiotic relationships among different cells and organisms. In addition, the ability of GS to predict patterns of glutamine metabolism and dependency among tumors is also crucial in the rational design and application of glutamine and other metabolic pathway targeted therapies. PMID:21852960

[Gorlin-Goltz syndrome: review of the neuroradiological and maxillofacial features illustrated with two clinical cases].

PubMed

Safronova, Marta Maia; Arantes, Mavilde; Lima, Iva; Domingues, Sara; Almeida, Marta; Moniz, Pedro

2010-01-01

Gorlin-Goltz syndrome or nevoid basal cell carcinoma syndrome is a rare hereditary autosomal-dominant disorder characterized by multiple basal cell carcinomas in young patients, odontogenic keratocysts, palmar or plantar pits, calcification of the falx cerebri and skeletal malformations. This syndrome is due to mutations in PTCH1 (patched homolog 1 da Drosophila), a tumor suppressor gene. Diagnostic criteria were defined by Evans, revised by Kimonis and include major and minor criteria. The authors review in particular the neuroradiological and maxillofacial characteristics of the syndrome. The authors describe the clinical presentation of two children with Gorlin-Goltz syndrome without affected first degree relatives. In both the clinical suspicion of the syndrome is raised by the presence of multiple odontogenic cysts surgically removed. Histopathological exam revealed keratocysts. None of the patients has basal cell carcinomas but both present with skeletal anomalies, namely marked pectus deformity. The absence of major diagnostic criteria like basal cell carcinomas or palmar or plantar pits in young patients delay the early diagnosis and the correct screening for medulloblastoma, basal cell carcinomas and cardiac fibromas. Odontogenic keratocysts are the most consistent clinical finding in Gorlin-Goltz syndrome in the first one or two decades of life. These patients are very sensitive to ionizing radiation, being able to develop basal cell carcinomas and meningiomas. Treatment should accomplish the complete resection of the tumors.

Measurement of In Vivo Three-Dimensional Corneal Cell Density and Size Using Two-Photon Imaging in C57BL/6 Mice.

PubMed

Zhang, Hongmin; He, Siyu; Liu, Susu; Xie, Yanting; Chen, Guoming; Zhang, Junjie; Sun, Shengtao; Liang, David; Wang, Liya

2016-04-01

To measure the cell size and cell density in five layers of the central cornea in the widely used inbred C57BL/6 mouse strain using in vivo three-dimensional (3D) two-photon (2PH) imaging. Corneas were scanned using a 2PH laser scanning fluorescence microscope after staining with plasma membrane stain and Hoechst 33342. Good quality 3D images were selected for the cell density and cell size analysis. Cell density was determined by counting the cell nuclei in a predefined cube of 3D images. Cell size measurements, including cell surface area, cell volume, nuclear surface area and nuclear volume, were automatically quantified using the Imaris software. The cell and nuclear surface-area-to-volume ratio (S:V ratio) and the cell nuclear-cytoplasmic ratio (N:C ratio) were calculated. The highest cell density was observed in the basal epithelium and the lowest in the posterior stroma. The highest cell surface area was found in the anterior stroma, and the highest cell volume was observed in the superficial epithelium. The lowest cell surface area and cell volume were both found in the basal epithelium. The highest S:V ratio was observed in the basal epithelium and the lowest in the superficial epithelium. The highest cell nuclear surface area and volume were both observed in the superficial epithelium and the lowest in the basal epithelium. The highest cell nuclear S:V ratio was observed in the basal epithelium and the lowest in the superficial epithelium. The highest N:C ratio was found in the basal epithelial cells and the lowest in the posterior keratocytes. We are the first to quantify the cell density and size parameters, including cell surface area and volume, cell nuclear surface area and volume, and the S:V ratio, in the five layers of the central cornea. These data provide important cell morphology features for the study of corneal physiology, pathology and disease in mice, particularly in C57BL/6 mice.

Differentiation of a Highly Tumorigenic Basal Cell Compartment in Urothelial Carcinoma

PubMed Central

He, Xiaobing; Marchionni, Luigi; Hansel, Donna E.; Yu, Wayne; Sood, Akshay; Yang, Jie; Parmigiani, Giovanni; Matsui, William; Berman, David M.

2011-01-01

Highly tumorigenic cancer cell (HTC) populations have been identified for a variety of solid tumors and assigned stem cell properties. Strategies for identifying HTCs in solid tumors have been primarily empirical rather than rational, particularly in epithelial tumors, which are responsible for 80% of cancer deaths. We report evidence for a spatially restricted bladder epithelial (urothelial) differentiation program in primary urothelial cancers (UCs) and in UC xenografts. We identified a highly tumorigenic UC cell compartment that resembles benign urothelial stem cells (basal cells), co-expresses the 67-kDa laminin receptor and the basal cell-specific cytokeratin CK17, and lacks the carcinoembryonic antigen family member CEACAM6 (CD66c). This multipotent compartment resides at the tumor-stroma interface, is easily identified on histologic sections, and possesses most, if not all, of the engraftable tumor-forming ability in the parental xenograft. We analyzed differential expression of genes and pathways in basal-like cells versus more differentiated cells. Among these, we found significant enrichment of pathways comprising “hallmarks” of cancer, and pharmacologically targetable signaling pathways, including Janus kinase-signal transducer and activator of transcription, Notch, focal adhesion, mammalian target of rapamycin, epidermal growth factor receptor (erythroblastic leukemia viral oncogene homolog [ErbB]), and wingless-type MMTV integration site family (Wnt). The basal/HTC gene expression signature was essentially invisible within the context of nontumorigenic cell gene expression and overlapped significantly with genes driving progression and death in primary human UC. The spatially restricted epithelial differentiation program described here represents a conceptual advance in understanding cellular heterogeneity of carcinomas and identifies basal-like HTCs as attractive targets for cancer therapy. PMID:19544456

Integrin signalling regulates YAP and TAZ to control skin homeostasis.

PubMed

Elbediwy, Ahmed; Vincent-Mistiaen, Zoé I; Spencer-Dene, Bradley; Stone, Richard K; Boeing, Stefan; Wculek, Stefanie K; Cordero, Julia; Tan, Ee H; Ridgway, Rachel; Brunton, Val G; Sahai, Erik; Gerhardt, Holger; Behrens, Axel; Malanchi, Ilaria; Sansom, Owen J; Thompson, Barry J

2016-05-15

The skin is a squamous epithelium that is continuously renewed by a population of basal layer stem/progenitor cells and can heal wounds. Here, we show that the transcription regulators YAP and TAZ localise to the nucleus in the basal layer of skin and are elevated upon wound healing. Skin-specific deletion of both YAP and TAZ in adult mice slows proliferation of basal layer cells, leads to hair loss and impairs regeneration after wounding. Contact with the basal extracellular matrix and consequent integrin-Src signalling is a key determinant of the nuclear localisation of YAP/TAZ in basal layer cells and in skin tumours. Contact with the basement membrane is lost in differentiating daughter cells, where YAP and TAZ become mostly cytoplasmic. In other types of squamous epithelia and squamous cell carcinomas, a similar control mechanism is present. By contrast, columnar epithelia differentiate an apical domain that recruits CRB3, Merlin (also known as NF2), KIBRA (also known as WWC1) and SAV1 to induce Hippo signalling and retain YAP/TAZ in the cytoplasm despite contact with the basal layer extracellular matrix. When columnar epithelial tumours lose their apical domain and become invasive, YAP/TAZ becomes nuclear and tumour growth becomes sensitive to the Src inhibitor Dasatinib. © 2016. Published by The Company of Biologists Ltd.

Integrin signalling regulates YAP and TAZ to control skin homeostasis

PubMed Central

Elbediwy, Ahmed; Vincent-Mistiaen, Zoé I.; Spencer-Dene, Bradley; Stone, Richard K.; Boeing, Stefan; Wculek, Stefanie K.; Cordero, Julia; Tan, Ee H.; Ridgway, Rachel; Brunton, Val G.; Sahai, Erik; Gerhardt, Holger; Behrens, Axel; Malanchi, Ilaria; Sansom, Owen J.; Thompson, Barry J.

2016-01-01

ABSTRACT The skin is a squamous epithelium that is continuously renewed by a population of basal layer stem/progenitor cells and can heal wounds. Here, we show that the transcription regulators YAP and TAZ localise to the nucleus in the basal layer of skin and are elevated upon wound healing. Skin-specific deletion of both YAP and TAZ in adult mice slows proliferation of basal layer cells, leads to hair loss and impairs regeneration after wounding. Contact with the basal extracellular matrix and consequent integrin-Src signalling is a key determinant of the nuclear localisation of YAP/TAZ in basal layer cells and in skin tumours. Contact with the basement membrane is lost in differentiating daughter cells, where YAP and TAZ become mostly cytoplasmic. In other types of squamous epithelia and squamous cell carcinomas, a similar control mechanism is present. By contrast, columnar epithelia differentiate an apical domain that recruits CRB3, Merlin (also known as NF2), KIBRA (also known as WWC1) and SAV1 to induce Hippo signalling and retain YAP/TAZ in the cytoplasm despite contact with the basal layer extracellular matrix. When columnar epithelial tumours lose their apical domain and become invasive, YAP/TAZ becomes nuclear and tumour growth becomes sensitive to the Src inhibitor Dasatinib. PMID:26989177

Dynamic thiol/disulphide homeostasis in patients with basal cell carcinoma.

PubMed

Demirseren, Duriye Deniz; Cicek, Cagla; Alisik, Murat; Demirseren, Mustafa Erol; Aktaş, Akın; Erel, Ozcan

2017-09-01

The aim of this study is to measure and compare the dynamic thiol/disulphide homeostasis of patients with basal cell carcinoma and healthy subjects with a newly developed and original method. Thirty four patients attending our outpatient clinic and clinically and histopathologically diagnosed as nodular basal cell carcinoma, and age and gender matched 30 healthy individuals have been involved in the study. Thiol/disulphide homeostasis tests have been measured with a novel automatic spectrophotometric method developed and the results have been compared statistically. Serum native thiol and disulphide levels in the patient and control group show a considerable variance statistically (p = 0.028, 0.039, respectively). Total thiol levels do not reveal a considerable variation (p = 0.094). Disulphide/native thiol ratios and native thiol/total thiol ratios also show a considerable variance statistically (p = 0.012, 0.013, 0.010, respectively). Thiol disulphide homeostasis in patients with basal cell carcinoma alters in the way that disulphide gets lower and thiols get higher. Thiol/disulphide level is likely to have a role in basal cell carcinoma pathogenesis.

Usefulness of (18)F-FDG PET/CT in recurrent basal cell carcinoma: Report of a case.

PubMed

Ayala, S; Perlaza, P; Puig, S; Prats, E; Vidal-Sicart, S

2016-01-01

We analyze the case of a patient with left periorbital infiltrating basal cell carcinoma treated with surgical excision in October 2010. Surgery included orbital exenteration and reconstruction using skin graft and radiotherapy. In May 2013 a MR imaging showed a mass in the left orbital fossa, suggesting a recurrence in the graft. A basal cell carcinoma recurrence with perineural invasion was confirmed in the biopsy. On (18)F-FDG PET/CT performed, a hypermetabolic activity was observed in the left periorbital area with extension to surrounding sinus and bones. The use of (18)F-FDG PET/CT in patients with advanced basal cell carcinoma has not been fully explored due to the rarity of this entity. This case demonstrates the usefulness of this technique to determine the extent of non-melanocytic recurrent skin tumors, and its value in the staging and treatment control, supporting the incorporation of (18)F-FDG PET/CT in the management of advanced basal cell carcinoma. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Partial denervation of sub-basal axons persists following debridement wounds to the mouse cornea.

PubMed

Pajoohesh-Ganji, Ahdeah; Pal-Ghosh, Sonali; Tadvalkar, Gauri; Kyne, Briana M; Saban, Daniel R; Stepp, Mary Ann

2015-11-01

Although sensory reinnervation occurs after injury in the peripheral nervous system, poor reinnervation in the elderly and those with diabetes often leads to pathology. Here we quantify sub-basal axon density in the central and peripheral mouse cornea over time after three different types of injury. The mouse cornea is highly innervated with a dense array of sub-basal nerves that form a spiral called the vortex at the corneal center or apex; these nerves are readily detected within flat mounted corneas. After anesthesia, corneal epithelial cells were removed using either a dulled blade or a rotating burr within an area demarcated centrally with a 1.5 mm trephine. A third wound type, superficial trephination, involved demarcating the area with the 1.5 mm trephine but not removing cells. By 7 days after superficial trephination, sub-basal axon density returns to control levels; by 28 days the vortex reforms. Although axon density is similar to control 14 days after dulled blade and rotating burr wounding, defects in axon morphology at the corneal apex remain. After 14 days, axons retract from the center leaving the sub-basal axon density reduced by 37.2 and 36.8% at 28 days after dulled blade and rotating burr wounding, respectively, compared with control. Assessment of inflammation using flow cytometry shows that persistent inflammation is not a factor in the incomplete reinnervation. Expression of mRNAs encoding 22 regeneration-associated genes involved in axon targeting assessed by QPCR reveals that netrin-1 and ephrin signaling are altered after wounding. Subpopulations of corneal epithelial basal cells at the corneal apex stop expressing ki67 as early as 7 days after injury and by 14 and 28 days after wounding, many of these basal cells undergo apoptosis and die. Although sub-basal axons are restored to their normal density and morphology after superficial trephination, sub-basal axon recovery is partial after debridement wounds. The increase in corneal epithelial basal cell apoptosis at the apex observed at 14 days after corneal debridement may destabilize newly reinnervated sub-basal axons and lead to their retraction toward the periphery.

Quantitative expression analysis of selected transcription factors in pavement, basal and trichome cells of mature leaves from Arabidopsis thaliana

PubMed Central

Schliep, Martin; Ebert, Berit; Simon-Rosin, Ulrike; Zoeller, Daniela

2010-01-01

Gene expression levels of several transcription factors from Arabidopsis thaliana that were described previously to be involved in leaf development and trichome formation were analysed in trichome, basal and pavement cells of mature leaves. Single cell samples of these three cells types were collected by glass micro-capillaries. Real-time reverse transcription (RT)-PCR was used to analyse expression patterns of the following transcription factors: MYB23, MYB55, AtHB1, FILAMENTOUS FLOWER (FIL)/YABBY1 (YAB1), TRIPTYCHON (TRY) and CAPRICE (CPC). A difference in the expression patterns of TRY and CPC was revealed. Contrary to the CPC expression pattern, no transcripts of TRY could be detected in pavement cells. FIL/YAB1 was exclusively expressed in trichome cells. AtHB1 was highly expressed throughout all three cell types. MYB55 was higher expressed in basal cells than in trichome and pavement cells. MYB23 showed a pattern of low expression in pavement cells, medium in basal cells and high expression in trichomes. Expression patterns obtained by single cell sampling and real-time RT-PCR were compared to promoter GUS fusions of the selected transcription factors. Therefore, we regenerated two transgenic Arabidopsis lines that expressed the GUS reporter gene under control of the promoters of MYB55 and YAB1. In conclusion, despite their function in leaf morphogenesis, all six transcription factors were detected in mature leaves. Furthermore, single cell sampling and promoter GUS staining patterns demonstrated the predominant presence of MYB55 in basal cells as compared to pavement cells and trichomes. PMID:20101514

Quantitative expression analysis of selected transcription factors in pavement, basal and trichome cells of mature leaves from Arabidopsis thaliana.

PubMed

Schliep, Martin; Ebert, Berit; Simon-Rosin, Ulrike; Zoeller, Daniela; Fisahn, Joachim

2010-05-01

Gene expression levels of several transcription factors from Arabidopsis thaliana that were described previously to be involved in leaf development and trichome formation were analysed in trichome, basal and pavement cells of mature leaves. Single cell samples of these three cells types were collected by glass micro-capillaries. Real-time reverse transcription (RT)-PCR was used to analyse expression patterns of the following transcription factors: MYB23, MYB55, AtHB1, FILAMENTOUS FLOWER (FIL)/YABBY1 (YAB1), TRIPTYCHON (TRY) and CAPRICE (CPC). A difference in the expression patterns of TRY and CPC was revealed. Contrary to the CPC expression pattern, no transcripts of TRY could be detected in pavement cells. FIL/YAB1 was exclusively expressed in trichome cells. AtHB1 was highly expressed throughout all three cell types. MYB55 was higher expressed in basal cells than in trichome and pavement cells. MYB23 showed a pattern of low expression in pavement cells, medium in basal cells and high expression in trichomes. Expression patterns obtained by single cell sampling and real-time RT-PCR were compared to promoter GUS fusions of the selected transcription factors. Therefore, we regenerated two transgenic Arabidopsis lines that expressed the GUS reporter gene under control of the promoters of MYB55 and YAB1. In conclusion, despite their function in leaf morphogenesis, all six transcription factors were detected in mature leaves. Furthermore, single cell sampling and promoter GUS staining patterns demonstrated the predominant presence of MYB55 in basal cells as compared to pavement cells and trichomes.

DISTAG/TBCCd1 Is Required for Basal Cell Fate Determination in Ectocarpus[OPEN

PubMed Central

Godfroy, Olivier; Uji, Toshiki; Nagasato, Chikako; Colin, Sebastien; Mignerot, Laure; Motomura, Taizo

2017-01-01

Brown algae are one of the most developmentally complex groups within the eukaryotes. As in many land plants and animals, their main body axis is established early in development, when the initial cell gives rise to two daughter cells that have apical and basal identities, equivalent to shoot and root identities in land plants, respectively. We show here that mutations in the Ectocarpus DISTAG (DIS) gene lead to loss of basal structures during both the gametophyte and the sporophyte generations. Several abnormalities were observed in the germinating initial cell in dis mutants, including increased cell size, disorganization of the Golgi apparatus, disruption of the microtubule network, and aberrant positioning of the nucleus. DIS encodes a TBCCd1 protein, which has a role in internal cell organization in animals, Chlamydomonas reinhardtii, and trypanosomes. Our study highlights the key role of subcellular events within the germinating initial cell in the determination of apical/basal cell identities in a brown alga and emphasizes the remarkable functional conservation of TBCCd1 in regulating internal cell organization across extremely distant eukaryotic groups. PMID:29208703

Fluorescence spectroscopy for neoplasms control

NASA Astrophysics Data System (ADS)

Bratchenko, I. A.; Kristoforova, Yu. A.; Myakinin, O. O.; Artemyev, D. N.; Kozlov, S. V.; Moryatov, A. A.; Zakharov, V. P.

2016-04-01

Investigation of malignant skin tumors diagnosis was performed involving two setups for native tissues fluorescence control in visible and near infrared regions. Combined fluorescence analysis for skin malignant melanomas and basal cell carcinomas was performed. Autofluorescence spectra of normal skin and oncological pathologies stimulated by 457 nm and 785 nm lasers were registered for 74 skin tissue samples. Spectra of 10 melanomas and 27 basal cell carcinomas were registered ex vivo. Skin tumors analysis was made on the basis of autofluorescence spectra intensity and curvature for analysis of porphyrins, lipo-pigments, flavins and melanin. Separation of melanomas and basal cell carcinomas was performed on the basis of discriminant analysis. Overall accuracy of basal cell carcinomas and malignant melanomas separation in current study reached 86.5% with 70% sensitivity and 92.6% specificity.

R-spondin3 is associated with basal-progenitor behavior in normal and tumor mammary cells.

PubMed

Tocci, Johanna Melisa; Felcher, Carla María; García Solá, Martín E; Goddio, María Victoria; Zimberlin, María Noel; Rubinstein, Natalia; Srebrow, Anabella; Coso, Omar Adrián; Abba, Martín C; Meiss, Roberto P; Kordon, Edith C

2018-05-10

R-spondin3 (RSPO3) is a member of a family of secreted proteins that enhance Wnt signaling pathways in diverse processes including cancer. However, the role of RSPO3 in mammary gland and breast cancer development remains unclear. In this study, we show that RSPO3 is expressed in the basal stem cell-enriched compartment of normal mouse mammary glands but is absent from committed mature luminal cells in which exogenous RSPO3 impairs lactogenic differentiation. RSPO3 knockdown in basal-like mouse mammary tumor cells reduced canonical Wnt signaling, epithelial-to-mesenchymal transition-like features, migration capacity, and tumor formation in vivo. Conversely, RSPO3 overexpression, which was associated with some LGR and RUNX factors, highly correlated with the basal-like subtype among breast cancer patients. Thus we identified RSPO3 as a novel key modulator of breast cancer development and a potential target for treatment of basal-like breast cancers. Copyright ©2018, American Association for Cancer Research.

Coexistence of mucous retention cyst and basal cell adenoma arising from the lining epithelium of the cyst. Report of two cases.

PubMed

Antoniades, D; Epivatianos, A; Markopoulos, A; Kolokotronis, A; Zaraboukas, T

2009-01-01

To report 2 cases of coexisting mucous retention cyst and basal cell adenoma arising from the lining epithelium of the cyst. Two cases of painless swellings, well-demarcated, soft to palpation, and located in the submucosa of the upper lip were clinically examined with the provisional diagnosis of mucocele or salivary gland tumor. Histological examination showed the presence of a large unilocular cystic cavity in many parts surrounded by single or bilayered lining epithelium composed of flattened to cuboidal cells, and in other parts surrounded by projections of cells arranged in a trabecular pattern far into the cystic cavity. The trabeculae were composed of basal and low columnar cells that sometimes formed small duct-like structures. Immunohistochemistry showed that the lining epithelium of the cystic cavity and the cells of the projections expressed cytokeratin 7 and high-molecular-weight cytokeratins. The cells of the projections were weakly positive for S-100 protein and negative for vimentin and alpha-smooth muscle actin. Based on the results, a diagnosis of coexisting mucous retention cysts and basal cell adenomas arising from the lining epithelium of cysts was made. The coexistence of mucous retention cysts and basal cell adenomas arising from the lining epithelium of the cyst is reported. Copyright 2009 S. Karger AG, Basel.

Long-lived keratin 15+ esophageal progenitor cells contribute to homeostasis and regeneration

PubMed Central

Giroux, Véronique; Lento, Ashley A.; Islam, Mirazul; Pitarresi, Jason R.; Kharbanda, Akriti; Hamilton, Kathryn E.; Whelan, Kelly A.; Long, Apple; Rhoades, Ben; Tang, Qiaosi; Nakagawa, Hiroshi; Lengner, Christopher J.; Bass, Adam J.; Wileyto, E. Paul; Klein-Szanto, Andres J.; Wang, Timothy C.; Rustgi, Anil K.

2017-01-01

The esophageal lumen is lined by a stratified squamous epithelium comprised of proliferative basal cells that differentiate while migrating toward the luminal surface and eventually desquamate. Rapid epithelial renewal occurs, but the specific cell of origin that supports this high proliferative demand remains unknown. Herein, we have described a long-lived progenitor cell population in the mouse esophageal epithelium that is characterized by expression of keratin 15 (Krt15). Genetic in vivo lineage tracing revealed that the Krt15 promoter marks a long-lived basal cell population able to self-renew, proliferate, and generate differentiated cells, consistent with a progenitor/stem cell population. Transcriptional profiling demonstrated that Krt15+ basal cells are molecularly distinct from Krt15– basal cells. Depletion of Krt15-derived cells resulted in decreased proliferation, thereby leading to atrophy of the esophageal epithelium. Further, Krt15+ cells were radioresistant and contributed to esophageal epithelial regeneration following radiation-induced injury. These results establish the presence of a long-lived and indispensable Krt15+ progenitor cell population that provides additional perspective on esophageal epithelial biology and the widely prevalent diseases that afflict this epithelium. PMID:28481227

An Interesting Case of Basal Cell Carcinoma with Raynaud's Phenomenon Following Chronic Arsenic Exposure.

PubMed

Gulshan, S; Rahman, M J; Sarkar, R; Ghosh, S; Hazra, R

2016-01-01

Arsenic is commonly known to be associated with squamous cell carcinoma. Among the lesser known associations is basal cell carcinoma and even rarer is its effect on blood vessels causing peripheral vascular disease. Here we present a case of a 55 yr old man with ulceroproliferative lesions on scalp and forehead along with several hyperpigmented patches on trunk and extremities. He had symptoms suggestive of Raynaud's phenomenon that eventually led to digital gangrene. FNAC was done which was suggestive of basal cell carcinoma. On further enquiry, he was found to reside in an arsenic endemic zone and was investigated for blood arsenic level which was elevated. Punch biopsy from different lesions from body confirmed nodular basal cell carcinoma. Presently the patient has stopped drinking water from the local tubewell. On follow-up he shows improvement of Raynaud's phenomenon and skin lesions.

Lachrymal Gland Basal Cell Adenocarcinoma in a Ferret (Mustela putorius furo).

PubMed

Chambers, J K; Nakamori, T; Kishimoto, T E; Nakata, M; Miwa, Y; Nakayama, H; Uchida, K

2016-01-01

A 1 cm diameter mass was detected in the caudal superotemporal area of the left eye of a 6-year-old neutered male ferret (Mustela putorius furo). The mass and the left eye were removed surgically. Microscopical examination revealed a tumour of the adnexal gland of the eye that had invaded the surrounding ocular muscle. The tumour was composed of basal-type epithelial cells arranged in a solid, or occasionally tubular, pattern. Immunohistochemically, the tumour cells expressed cytokeratin and p63, but not smooth muscle actin. Based on these findings, the tumour was diagnosed as a basal cell adenocarcinoma of the lachrymal gland. In addition to the tumour, the retina of the left eye was detached and folded at the centre of the globe. This is the first report of a non-human case of basal cell adenocarcinoma of the lachrymal gland. Copyright © 2016 Elsevier Ltd. All rights reserved.

Basal cell carcinoma

MedlinePlus

... confirm basal cell cancer or other skin cancers. Treatment Treatment depends on the size, depth, and location ... blocks both UVA and UVB light. Use a water-resistant sunscreen. Apply sunscreen at least 30 minutes ...

[Basal cell carcinoma among the cases of Dermatology Clinic I of the Silesian Medical Academy in Katowice].

PubMed

Bogdanowski, T; Rubisz-Brzezińska, J; Sleczka, A

1988-01-01

The authors present their own experiences in the treatment of 24 patients with the nevoid basal-cell carcinoma syndrome. All the patients underwent surgical treatment, in 12 of them some of the tumours were treated with X-rays. Two patients were found to have 32 and 26 nevoid basal-cell carcinoma respectively. In none of the 24 patients recurrence was noted. However in many of them the new foci of carcinoma required systemic treatment.

Basal cell carcinomas in elderly patients treated by cryotherapy

PubMed Central

Chiriac, Anca; Mihaila, Doina; Foia, Liliana; Solovan, Caius

2013-01-01

Basal cell carcinoma is a malignant skin tumor with high incidence in our country, especially in rural areas, on sun-exposed skin (particularly on the face) in elderly patients. We present three cases of basal cell carcinoma with good results with cryotherapy. This report aims to outline and to prove that in some difficult situations, a simple, inexpensive, easy-to-perform procedure with no contraindications and with minimal side effects (erythema, mild pain) can be applied and resolve such cases. PMID:23569366

Primary squamous cell carcinoma of the breast with unusual basal-HER2 phenotype.

PubMed

Shui, Ruohong; Li, Anqi; Yang, Fei; Zhou, Xiaoyan; Yu, Baohua; Xu, Xiaoli; Yang, Wentao

2014-01-01

To report three cases of primary squamous cell carcinoma of the breast with an unusual "basal-HER2" phenotype. Clinical data were analyzed. Morphological features were observed. Immunohistochemical study for ER, PR, HER2, Ki-67, CK 5/6, CK10/13, CK14, EGFR, P63 and FISH detection of HER2 gene amplification were performed. Three patients were all female with 26, 57 and 66 years old. The tumors were 3 cm, 4 cm and 5 cm in size respectively. Morphologically, all three tumors were pure squamous cell carcinoma and entirely composed metaplastic squamous cells. Two tumors were moderately differentiated and one was poorly differentiated. All three patients were positive for P63 or CK10/13. All three tumors exhibited basal-HER2 phenotype: negative for ER and PR, positive for HER2 protein and HER2 gene amplification, and positive for at least two basal markers. SCC with basal-HER2 phenotype is an extremely rare subset of breast carcinoma. Since it may have worse prognosis than typical basal-like SCC, recognization of this unusual SCC in routine work may have obvious clinical significance.

s-SHIP expression identifies a subset of murine basal prostate cells as neonatal stem cells

PubMed Central

Brocqueville, Guillaume; Chmelar, Renee S.; Bauderlique-Le Roy, Hélène; Deruy, Emeric; Tian, Lu; Vessella, Robert L.; Greenberg, Norman M.; Bourette, Roland P.

2016-01-01

Isolation of prostate stem cells (PSCs) is crucial for understanding their biology during normal development and tumorigenesis. In this aim, we used a transgenic mouse model expressing GFP from the stem cell-specific s-SHIP promoter to mark putative stem cells during postnatal prostate development. Here we show that cells identified by GFP expression are present transiently during early prostate development and localize to the basal cell layer of the epithelium. These prostate GFP+ cells are a subpopulation of the Lin− CD24+ Sca-1+ CD49f+ cells and are capable of self-renewal together with enhanced growth potential in sphere-forming assay in vitro, a phenotype consistent with that of a PSC population. Transplantation assays of prostate GFP+ cells demonstrate reconstitution of prostate ducts containing both basal and luminal cells in renal grafts. Altogether, these results demonstrate that s-SHIP promoter expression is a new marker for neonatal basal prostate cells exhibiting stem cell properties that enables PSCs in situ identification and isolation via a single consistent parameter. Transcriptional profiling of these GFP+ neonatal stem cells showed an increased expression of several components of the Wnt signaling pathway. It also identified stem cell regulators with potential applications for further analyses of normal and cancer stem cells. PMID:27081082

General statistics of stochastic process of gene expression in eukaryotic cells.

PubMed Central

Kuznetsov, V A; Knott, G D; Bonner, R F

2002-01-01

Thousands of genes are expressed at such very low levels (< or =1 copy per cell) that global gene expression analysis of rarer transcripts remains problematic. Ambiguity in identification of rarer transcripts creates considerable uncertainty in fundamental questions such as the total number of genes expressed in an organism and the biological significance of rarer transcripts. Knowing the distribution of the true number of genes expressed at each level and the corresponding gene expression level probability function (GELPF) could help resolve these uncertainties. We found that all observed large-scale gene expression data sets in yeast, mouse, and human cells follow a Pareto-like distribution model skewed by many low-abundance transcripts. A novel stochastic model of the gene expression process predicts the universality of the GELPF both across different cell types within a multicellular organism and across different organisms. This model allows us to predict the frequency distribution of all gene expression levels within a single cell and to estimate the number of expressed genes in a single cell and in a population of cells. A random "basal" transcription mechanism for protein-coding genes in all or almost all eukaryotic cell types is predicted. This fundamental mechanism might enhance the expression of rarely expressed genes and, thus, provide a basic level of phenotypic diversity, adaptability, and random monoallelic expression in cell populations. PMID:12136033

TP53 supports basal-like differentiation of mammary epithelial cells by preventing translocation of deltaNp63 into nucleoli

NASA Astrophysics Data System (ADS)

Munne, Pauliina M.; Gu, Yuexi; Tumiati, Manuela; Gao, Ping; Koopal, Sonja; Uusivirta, Sanna; Sawicki, Janet; Wei, Gong-Hong; Kuznetsov, Sergey G.

2014-04-01

Multiple observations suggest a cell type-specific role for TP53 in mammary epithelia. We developed an in vitro assay, in which primary mouse mammary epithelial cells (mMECs) progressed from lumenal to basal-like phenotypes based on expression of Krt18 or ΔNp63, respectively. Such transition was markedly delayed in Trp53-/- mMECs suggesting that Trp53 is required for specification of the basal, but not lumenal cells. Evidence from human basal-like cell lines suggests that TP53 may support the activity of ΔNp63 by preventing its translocation from nucleoplasm into nucleoli. In human lumenal cells, activation of TP53 by inhibiting MDM2 or BRCA1 restored the nucleoplasmic expression of ΔNp63. Trp53-/- mMECs eventually lost epithelial features resulting in upregulation of MDM2 and translocation of ΔNp63 into nucleoli. We propose that TP63 may contribute to TP53-mediated oncogenic transformation of epithelial cells and shed light on tissue- and cell type-specific biases observed for TP53-related cancers.

TP53 supports basal-like differentiation of mammary epithelial cells by preventing translocation of deltaNp63 into nucleoli.

PubMed

Munne, Pauliina M; Gu, Yuexi; Tumiati, Manuela; Gao, Ping; Koopal, Sonja; Uusivirta, Sanna; Sawicki, Janet; Wei, Gong-Hong; Kuznetsov, Sergey G

2014-04-11

Multiple observations suggest a cell type-specific role for TP53 in mammary epithelia. We developed an in vitro assay, in which primary mouse mammary epithelial cells (mMECs) progressed from lumenal to basal-like phenotypes based on expression of Krt18 or ΔNp63, respectively. Such transition was markedly delayed in Trp53(-/-) mMECs suggesting that Trp53 is required for specification of the basal, but not lumenal cells. Evidence from human basal-like cell lines suggests that TP53 may support the activity of ΔNp63 by preventing its translocation from nucleoplasm into nucleoli. In human lumenal cells, activation of TP53 by inhibiting MDM2 or BRCA1 restored the nucleoplasmic expression of ΔNp63. Trp53(-/-) mMECs eventually lost epithelial features resulting in upregulation of MDM2 and translocation of ΔNp63 into nucleoli. We propose that TP63 may contribute to TP53-mediated oncogenic transformation of epithelial cells and shed light on tissue- and cell type-specific biases observed for TP53-related cancers.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morishige, Naoyuki; Ko, Ji-Ae, E-mail: jiae0831@yamaguchi-u.ac.jp; Morita, Yukiko

The neural guidance protein semaphorin 3A (Sema3A) is expressed in corneal epithelial cells of the adult rat. We have now further investigated the localization of Sema3A in the normal rat corneal epithelium as well as changes in its expression pattern during wound healing after central corneal epithelial debridement. The expression pattern of Sema3A was compared with that of the tight-junction protein zonula occludens-1 (ZO-1), the gap-junction protein connexin43 (Cx43), or the cell proliferation marker Ki67. Immunofluorescence analysis revealed that Sema3A was present predominantly in the membrane of basal and wing cells of the intact corneal epithelium. The expression of Sema3Amore » at the basal side of basal cells was increased in the peripheral epithelium compared with that in the central region. Sema3A was detected in all layers at the leading edge of the migrating corneal epithelium at 6 h after central epithelial debridement. The expression of Sema3A was markedly up-regulated in the basal and lateral membranes of columnar basal cells apparent in the thickened, newly healed epithelium at 1 day after debridement, but it had largely returned to the normal pattern at 3 days after debridement. The expression of ZO-1 was restricted to superficial epithelial cells and remained mostly unchanged during the wound healing process. The expression of Cx43 in basal cells was down-regulated at the leading edge of the migrating epithelium but was stable in the remaining portion of the epithelium. Ki67 was not detected in basal cells of the central epithelium at 1 day after epithelial debridement, when Sema3A was prominently expressed. Immunoblot analysis showed that the abundance of Sema3A in the central cornea was increased 1 day after epithelial debridement, whereas that of ZO-1 or Cx43 remained largely unchanged. This increase in Sema3A expression was accompanied by up-regulation of the Sema3A coreceptor neuropilin-1. Our observations have thus shown that the expression of Sema3A is increased markedly in basal cells of the newly healed corneal epithelium, and that this up-regulation of Sema3A is not associated with cell proliferation. They further suggest that Sema3A might play a role in the regulation of corneal epithelial wound healing.« less

Somatic embryogenesis and plant regeneration from cell suspension cultures of Cucumis sativus L.

PubMed

Chee, P P; Tricoli, D M

1988-06-01

A procedure for the regeneration of whole cucumber plants (Cucumis sativus L. cv. Poinsett 76) by embryogenesis from cell suspension cultures is described. Embryogenic callus was initiated from the primary leaves of 14-17 day old plants. Suspension cultures of embryogenic cells were grown in liquid Murashige and Skoog basal medium containing 5 uM 2,4,5-trichlorophenoxyacetic acid and 4 uM 6-benzylaminopurine. Suspension cultures were composed of a population of cells that were densely cytoplasmic and potentially embryogenic. Differentiation of embryos was enhanced by washing the suspension culture cells with MS basal medium containing 0.5% activated charcoal and twice with MS basal medium followed by liquid shake cultures in MS basal medium. Sixty to 70 percent of the embryos prewashed with activated charcoal germinated into plantlets with normal morphology. Embryos obtained from suspension cultured cells without prewashing with activated charcoal organized into plantlets with abnormal primary leaves. Morphologically normal plantlets were obtained by excising the shoot tips and transferring them to fresh medium.

Basal Forebrain Gating by Somatostatin Neurons Drives Prefrontal Cortical Activity.

PubMed

Espinosa, Nelson; Alonso, Alejandra; Morales, Cristian; Espinosa, Pedro; Chávez, Andrés E; Fuentealba, Pablo

2017-11-17

The basal forebrain provides modulatory input to the cortex regulating brain states and cognitive processing. Somatostatin-expressing neurons constitute a heterogeneous GABAergic population known to functionally inhibit basal forebrain cortically projecting cells thus favoring sleep and cortical synchronization. However, it remains unclear if somatostatin cells can regulate population activity patterns in the basal forebrain and modulate cortical dynamics. Here, we demonstrate that somatostatin neurons regulate the corticopetal synaptic output of the basal forebrain impinging on cortical activity and behavior. Optogenetic inactivation of somatostatin neurons in vivo rapidly modified neural activity in the basal forebrain, with the consequent enhancement and desynchronization of activity in the prefrontal cortex, reflected in both neuronal spiking and network oscillations. Cortical activation was partially dependent on cholinergic transmission, suppressing slow waves and potentiating gamma oscillations. In addition, recruitment dynamics was cell type-specific, with interneurons showing similar temporal profiles, but stronger responses than pyramidal cells. Finally, optogenetic stimulation of quiescent animals during resting periods prompted locomotor activity, suggesting generalized cortical activation and increased arousal. Altogether, we provide physiological and behavioral evidence indicating that somatostatin neurons are pivotal in gating the synaptic output of the basal forebrain, thus indirectly controlling cortical operations via both cholinergic and non-cholinergic mechanisms. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Basal cell adenocarcinoma in the gland of the third eyelid of a brown bear (Ursus arctos)

PubMed Central

SAKAI, Hiroki; GOTO, Minami; KOMATSU, Takeshi

2017-01-01

The right third eyelid of an adult female brown bear (c) was swollen and removed. Histopathology revealed a tumor exhibiting proliferation with mild infiltration, consisting of multi-stratified glandular structures of the innermost laminal neoplastic cells and the basaloid neoplastic cells, and with eosinophilic thick basal lamina material around the glandular structures. Both types of neoplastic cells exhibited moderate anisokaryosis, and mitotic figures were observed in the basaloid neoplastic cells. The laminal neoplastic cells were cytokeratin (CK) 8/18-positive. In contrast, the basaloid neoplastic cells were CK14- and p63-positive, but α-smooth muscle actin- and calponin-negative. The case described herein is the first report of basal cell adenocarcinoma in the gland of the third eyelid of a bear. PMID:28637946

Predicting oak density with ecological, physical, and soil indicators

Treesearch

Callie Jo Schweitzer; Adrian A. Lesak; Yong Wang

2006-01-01

We predicted density of oak species in the mid-Cumberland Plateau region of northeastern Alabama on the basis of basal area of tree associations based on light tolerances, physical site characteristics, and soil type. Tree basal area was determined for four species groups: oaks (Quercus spp.), hickories (Carya spp.), yellow-poplar...

Orthovoltage X-rays for Postoperative Treatment of Resected Basal Cell Carcinoma in the Head and Neck Area.

PubMed

Duinkerken, Charlotte W; Lohuis, Peter J F M; Crijns, Marianne B; Navran, Arash; Haas, Rick L M; Hamming-Vrieze, Olga; Klop, W Martin C; van den Brekel, Michiel W M; Al-Mamgani, Abrahim

Surgery is the golden standard for treating basal cell carcinomas. In case of positive tumor margins or recurrent disease, postoperative adjuvant or salvaging therapy is suggested to achieve good local control. To retrospectively report on local control and toxicity of postoperative radiotherapy by means of orthovoltage X-rays for residual or recurrent basal cell carcinoma after surgery in the head and neck area. Sixty-six surgically resected residual or recurrent basal cell carcinomas of the head and neck region were irradiated postoperatively by means of orthovoltage X-rays at the Netherlands Cancer Institute between January 2000 and February 2015. After a median follow-up duration of 30.5 months, only 5 recurrences were reported. The 5-year local control rates at 1, 3, and 5 years were 100%, 87%, and 87%, respectively. The 5-year local control rate was 92% for immediate postoperative radiotherapy of incompletely resected basal cell carcinomas, 90% for recurrences after 1 previously performed excision, and 71% for multiple recurrences, namely, a history of more than 1 excision ( P = .437). Acute toxicity healed spontaneously within 3 months. Late toxicities were mild. Radiotherapy by means of orthovoltage X-ray is an excellent alternative for re-excision in case of incompletely resected or recurrent basal cell carcinomas that are at risk of serious functional and cosmetic impairments after re-excision, with a 5-year local control rate of 87% and a low toxicity profile.

Improved chemically defined basal medium (CMRL-1969) for primary monkey kidney and human diploid cells.

PubMed

Healy, G M; Teleki, S; von Seefried, A; Walton, M J; Macmorine, H G

1971-01-01

An improved tissue culture basal medium, CMRL-1969, supplemented with serum, has been evaluated by measuring the growth responses of primary cultures of trypsin-dispersed monkey kidney cells (PMKC) and of an established culture of a human diploid cell strain (HDCS). Medium H597, an early modification of medium 199 which has been used successfully in the preparation of poliomyelitis vaccine for 15 years, was used for comparison. In addition, parallel testing was done with Basal Medium Eagle (BME) widely used for the growth of HDCS. The improvements in basal medium CMRL-1969 are attributed to changes in amino acid concentrations, in vitamin composition, and, in particular, to enhanced buffering capacity. The latter has been achieved by the use of free-base amino acids and by increasing the dibasic sodium phosphate. The new medium has already been used to advantage for the production of polioviruses in PMKC where equivalent titers were obtained from cultures initiated with 70% of the number of cells required with earlier media. The population-doubling time was reduced in this system. Also, with small inocula of HDCS, the time required to obtain maximum cell yield was shorter with CMRL-1969 than with BME. Both media were supplemented with 10% calf serum. Maximum cell yields after repeated subcultivation in the new basal medium were greatly increased and the stability of the strain, as shown by chromosomal analysis, was not affected. Basal medium CMRL-1969 can be prepared easily in liquid or powdered form.

Basal Cell Carcinoma in Cases with or without Xeroderma Pigmentosum.

PubMed

Ghartimagar, Dilasma; Ghosh, Arnab; Shrestha, Sushil Ram; Shrestha, Sachet; Thapa, Sushma; Narasimhan, Raghavan; Talwar, O P

2017-01-01

Basal cell carcinoma is the most common form of cancer in humans and comprises the vast majority of skin cancers. It predominantly affects fair-skinned individuals, and its incidence is rapidly increasing. The objective of the study is to identify the epidemiology, its topography and different histological subtypes of basal cell carcinoma in patients with or without Xeroderma Pigmentosum. A cross-sectional descriptive study was conducted at Manipal Teaching Hospital, Pokhara from Jan 2009 to Dec 2016. Ethical approval was taken from MEMG/IRC/GA. The study included patients with a confirmed diagnosis of basal cell carcinoma irrespective of their age and sex. This study showed 77 individuals with 91 biopsies of BCC including 5 cases of Xeroderma Pigmentosum. The predominant histological subtype was nodular with 41 (53.94%) cases, followed by the 14 (18.42%) cases of pigmented and 10 (13.15%) cases baso-squamous subtype. The most frequent sites of involvement were the head and neck, with predominance in the nasal and orbital region. The mean age was 57.68 years but the basal cell carcinoma in cases of Xeroderma Pigmentosum was seen more in younger age groups. There were 43 (55.84 %) male patients and 34 (44.16 %) female patients with a male to female ratio of 1.26:1. Nodular and pigmented varieties were the most frequent subtypes with nose being the commonest site of involvement. Basal cell carcinomas in cases of Xeroderma Pigmentosum were noted in younger age group with multiple lesions.

A Rare Case of Giant Basal Cell Carcinoma of the Abdominal Wall: Excision and Immediate Reconstruction with a Pedicled Deep Inferior Epigastric Artery Perforator (DIEP) Flap

PubMed Central

Di Lorenzo, Sara; Zabbia, Giovanni; Corradino, Bartolo; Tripoli, Massimiliano; Pirrello, Roberto; Cordova, Adriana

2017-01-01

Patient: Female, 82 Final Diagnosis: Giant basal cell carcinoma Symptoms: Anemia Medication: — Clinical Procedure: — Specialty: Plastic Surgery Objective: Rare disease Background: Basal cell carcinoma (BCC) greater than 5 cm in diameter is called giant basal cell carcinoma (GBCC), or super giant basal cell carcinoma if it has a diameter larger than 20 cm. Giant BCC only accounts for 0.5% of BCCs and super giant BCC is exceedingly rare. On account of their rarity, there are no established guidelines for GBCC treatment. Case Report: We describe a peculiar case of an 82-year-old woman with a GBCC carcinoma of the lower abdominal wall. The tumor was surgically removed with ipsilateral inguinal lymph nodes and the abdominal wall was reconstructed immediately with a pedicled deep inferior epigastric artery perforator (DIEP) flap. Conclusions: Treatment of giant basal cell carcinoma is often difficult, especially in elderly patients with poor general health and multiple pathologies. The pedicled DIEP flap is rotated to cover the loss of substance without tension, and it is easy to harvest and transfer. This flap allowed a good result without local or systemic complication. We present this report as a reminder of the occasional occurrence of extremely aggressive BCCs. We believe that, especially for rare tumors like these, it is very useful for the entire scientific community to publish these cases and the therapeutic strategies used to treat them. PMID:29199268

Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy

PubMed Central

Johnson, Douglas B.; Estrada, Monica V.; Salgado, Roberto; Sanchez, Violeta; Doxie, Deon B.; Opalenik, Susan R.; Vilgelm, Anna E.; Feld, Emily; Johnson, Adam S.; Greenplate, Allison R.; Sanders, Melinda E.; Lovly, Christine M.; Frederick, Dennie T.; Kelley, Mark C.; Richmond, Ann; Irish, Jonathan M.; Shyr, Yu; Sullivan, Ryan J.; Puzanov, Igor; Sosman, Jeffrey A.; Balko, Justin M.

2016-01-01

Anti-PD-1 therapy yields objective clinical responses in 30–40% of advanced melanoma patients. Since most patients do not respond, predictive biomarkers to guide treatment selection are needed. We hypothesize that MHC-I/II expression is required for tumour antigen presentation and may predict anti-PD-1 therapy response. In this study, across 60 melanoma cell lines, we find bimodal expression patterns of MHC-II, while MHC-I expression was ubiquitous. A unique subset of melanomas are capable of expressing MHC-II under basal or IFNγ-stimulated conditions. Using pathway analysis, we show that MHC-II(+) cell lines demonstrate signatures of ‘PD-1 signalling', ‘allograft rejection' and ‘T-cell receptor signalling', among others. In two independent cohorts of anti-PD-1-treated melanoma patients, MHC-II positivity on tumour cells is associated with therapeutic response, progression-free and overall survival, as well as CD4+ and CD8+ tumour infiltrate. MHC-II+ tumours can be identified by melanoma-specific immunohistochemistry using commercially available antibodies for HLA-DR to improve anti-PD-1 patient selection. PMID:26822383

Expression of hemidesmosomal and extracellular matrix proteins by normal and malignant human prostate tissue.

PubMed Central

Nagle, R. B.; Hao, J.; Knox, J. D.; Dalkin, B. L.; Clark, V.; Cress, A. E.

1995-01-01

The progression of prostate carcinoma may be influenced by the biochemical nature of the basal lamina surrounding the primary carcinoma cells. As a first step toward understanding this process, the composition and structure of the basal lamina in normal prostate, prostatic intraepithelial neoplasia, and human carcinoma were determined. In addition, a comparison was made between the attachments of the normal basal cell to its underlying basal lamina and those made by primary prostate carcinoma. The normal basal cells form both focal adhesions and hemidesmosomal-like structures as observed by transmission electron microscopy. The normal basal cells exhibited a polarized distribution of hemidesmosomal associated proteins including BP180, BP230, HD1, plectin, laminin-gamma 2(B2t), collagen VII, and the corresponding integrin laminin receptors alpha 6 beta 1 and alpha 6 beta 4. The expression and distribution pattern of these proteins were retained in the prostate intraepithelial neoplasia lesions. In contrast, the carcinoma cells uniformly lacked hemidesmosomal structures, the integrin alpha 6 beta 4, BP180, laminin-gamma 2 (B2t), and collagen VII but did express BP230 (30%), plectin, HD1 (15%), and the integrin laminin receptors alpha 3 beta 1 and alpha 6 beta 1. These results suggest that, although a detectable basal lamina structure is present in carcinoma, its composition and cellular attachments are abnormal. The loss of critical cellular attachments may play a role in influencing the progression potential of prostate carcinoma. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7778688

Computational Tools and Resources for Metabolism-Related Property Predictions. 1. Overview of Publicly Available (Free and Commercial) Databases and Software

DTIC Science & Technology

2012-01-01

pathway inhibitor Smoothened GPCR Basal cell carcinoma Ivacaftor Kalydeco™ Vertex 203188 31 January 2012 CFTR potentiator CFTR chloride channel ...inhibitor Platelet P2Y 12 ADP-receptor Acute coronary syndrome Ezogabine Potiga™ GlaxoSmithKline/ Valeant 022345 10 June 2011 Potassium channel opener...KCNQ/ Kv7 Epilepsy Linagliptin Tradjenta® Boehringer Ingelheim 201280 2 May 2011 Peptidase inhibitor DPP-4 Type 2 diabetes Abiraterone Zytiga® Janssen

Dermal changes in superficial basal cell carcinoma, melanoma in situ and actinic keratosis and their implications

PubMed Central

Kazlouskaya, Viktoryia; Malhotra, Saurabh; Navarro, Raquel; Wu, Karen Nguyen; Shvartsbeyn, Marianna; Shengli, Chen; Gui, Jiang; Elston, Dirk M.

2018-01-01

Background Basal cell carcinoma (BCC) has a characteristic stroma, but less is known about the dermal characteristics associated with melanoma in situ (MIS) and actinic keratosis (AK). Materials and methods Dermal changes were studied in 301 specimens of AK, BCC and MIS. Subsequently, blinded images of dermal changes from 90 randomly selected cases of those entities were used to assess the predictive value of the dermal changes. Agreement with the final diagnosis was calculated using kappa coefficient (κ). Results Fibromyxoid stroma was present in 82% of BCC cases; fibrous stroma was seen in 25% of BCC, 58% of MIS and 35.6% of AK specimens (p <0.05). A lichenoid inflammatory infiltrate was frequently associated with AK and a perifollicular infiltrate with periadnexal fibrosis with MIS. Blinded evaluation of images of the dermal changes associated with the tumors yielded the correct diagnosis in (54.4, 41.1 and 27.8%; average 41.2%) by the three appraisers. Coefficient of agreement in blinded imaged evaluation with the actual diagnosis was higher in the BCC and MIS compared with AK (κ = 0.37, p = 0.0001; κ = 0.2, p = 0.0005 and κ = −0.06, p = 0.84, respectively). Conclusion Dermal features may be helpful in predicting the correct diagnosis when tumor is not visible. PMID:24117926

Nature of "basal" and "reserve" cells in oviductal and cervical epithelium in man.

PubMed Central

Peters, W M

1986-01-01

The epithelium of the human fallopian tube (oviduct) and cervix were studied by histological, immunohistological, and ultrastructural methods with a view to establishing the nature of the so called "basal" and "reserve" cells. The results indicated that the "basal" cells of the oviductal epithelia were T lymphocytes, with a predominance of T cytotoxic and suppressor cells. A more heterogeneous inflammatory cell population was present in cervical epithelium, although once again T cytotoxic and suppressor cells were the most numerous subtype. The intraepithelial inflammatory cells were quite distinct from the cells commonly referred to as "reserve" cells (reserve cell hyperplasia), which have epithelial characteristics. The origin of the "reserve" cells is unclear, but they seem to arise within the epithelium. They probably represent an early sign of squamous metaplasia. The lymphoid tissue of fallopian tube and endocervix shows similarities with that of the endometrium and mucosal associated lymphoid tissue in general. Images PMID:2937810

Discovery of Genes Expressed In Basal Endosperm Transfer Cells in Maize Using 454 Transcriptome Sequencing

USDA-ARS?s Scientific Manuscript database

Basal endosperm transfer cells (BETCs) constitute one of the four cell types in an endosperm with a major role in solute acquisition and transport functions from the mother plant. The BETCs with their wall-in-growth (WIG) feature that greatly increase plasma membrane area of each cell are critical f...

Absorbed dose in target cell nuclei and dose conversion coefficient of radon progeny in the human lung.

PubMed

Nikezic, D; Lau, B M F; Stevanovic, N; Yu, K N

2006-01-01

To calculate the absorbed dose in the human lung due to inhaled radon progeny, ICRP focussed on the layers containing the target cells, i.e., the basal and secretory cells. Such an approach did not consider details of the sensitive cells in the layers. The present work uses the microdosimetric approach and determines the absorbed alpha-particle energy in non-spherical nuclei of target cells (basal and secretory cells). The absorbed energy for alpha particles emitted by radon progeny in the human respiratory tract was calculated in basal- and secretory-cell nuclei, assuming conical and ellipsoidal forms for these cells. Distributions of specific energy for different combinations of alpha-particle sources, energies and targets are calculated and shown. The dose conversion coefficient for radon progeny is reduced for about 2mSv/WLM when conical and ellipsoidal cell nuclei are considered instead of the layers. While changes in the geometry of secretory-cell nuclei do not have significant effects on their absorbed dose, changes from spherical to conical basal-cell nuclei have significantly reduced their absorbed dose from approximately 4 to approximately 3mGy/WLM. This is expected because basal cells are situated close to the end of the range of 6MeV alpha particles. This also underlines the significance of better and more precise information on targets in the T-B tree. A further change in the dose conversion coefficient can be achieved if a different weighting scheme is adopted for the doses for the cells. The results demonstrate the necessity for better information on the target cells for more accurate dosimetry for radon progeny.

Enhanced systemic immune reactivity to a Basal cell carcinoma associated antigen following photodynamic therapy.

PubMed

Kabingu, Edith; Oseroff, Allan R; Wilding, Gregory E; Gollnick, Sandra O

2009-07-01

Numerous preclinical studies have shown that local photodynamic therapy (PDT) of tumors enhances systemic antitumor immunity. However, other than single-case and anecdotal reports, this phenomenon has not been examined following clinical PDT. To determine whether PDT in a clinical setting enhances systemic recognition of tumor cells, we examined whether PDT of basal cell carcinoma resulted in an increased systemic immune response to Hip1, a tumor antigen associated with basal cell carcinoma. Basal cell carcinoma lesions were either treated with PDT or surgically removed. Blood was collected from patients immediately before or 7 to 10 days following treatment. Peripheral blood leukocytes were isolated from HLA-A2-expressing patients and reactivity to a HLA-A2-restricted Hip1 peptide was measured by INF-gamma ELISpot assay. Immune recognition of Hip1 increased in patients whose basal cell carcinoma lesions were treated with PDT. This increase in reactivity was significantly greater than reactivity observed in patients whose lesions were surgically removed. Patients with superficial lesions exhibited greater enhancement of reactivity compared with patients with nodular lesions. Immune reactivity following PDT was inversely correlated with treatment area and light dose. These findings show for the first time that local tumor PDT can enhance systemic immune responses to tumors in patients, and validate previous preclinical findings.

Intra-lineage Fate Decisions Involve Activation of Notch Receptors Basal to the Midbody in Drosophila Sensory Organ Precursor Cells.

PubMed

Trylinski, Mateusz; Mazouni, Khalil; Schweisguth, François

2017-08-07

Notch receptors regulate cell fate decisions during embryogenesis and throughout adult life. In many cell lineages, binary fate decisions are mediated by directional Notch signaling between the two sister cells produced by cell division. How Notch signaling is restricted to sister cells after division to regulate intra-lineage decision is poorly understood. More generally, where ligand-dependent activation of Notch occurs at the cell surface is not known, as methods to detect receptor activation in vivo are lacking. In Drosophila pupae, Notch signals during cytokinesis to regulate the intra-lineage pIIa/pIIb decision in the sensory organ lineage. Here, we identify two pools of Notch along the pIIa-pIIb interface, apical and basal to the midbody. Analysis of the dynamics of Notch, Delta, and Neuralized distribution in living pupae suggests that ligand endocytosis and receptor activation occur basal to the midbody. Using selective photo-bleaching of GFP-tagged Notch and photo-tracking of photo-convertible Notch, we show that nuclear Notch is indeed produced by receptors located basal to the midbody. Thus, only a specific subset of receptors, located basal to the midbody, contributes to signaling in pIIa. This is the first in vivo characterization of the pool of Notch contributing to signaling. We propose a simple mechanism of cell fate decision based on intra-lineage signaling: ligands and receptors localize during cytokinesis to the new cell-cell interface, thereby ensuring signaling between sister cells, hence intra-lineage fate decision. Copyright © 2017 Elsevier Ltd. All rights reserved.

Differentiated epidermal outgrowths in the planarian Dugesia gonocephala: a model for studying cell renewal and patterning in single-layered epithelial tissue.

PubMed

Chandebois, R

1985-01-01

Large deep wounds on the ventral side of a flatworm (Planaria) will not heal. Instead, the damage to the parenchyma in the wound's roof will result in a differentiated swelling in the dorsal epidermis, above the wound which will eventually disappear with the disintegration of the underlying damaged tissue and a ventrodorsal hole appears in place of the wound. The dorsal epidermal outgrowth is formed by a number of excrescences, the development of which involves four successive stages. Their analysis suggests that epidermal cells are continuously produced by their own stem cells which remain unnoticed because their nuclei are hardly stainable. The daughter cells differentiate without information from either the underlying tissues or the basal epithelial membrane. During the first stage of this differentiation the cells become ciliated and motile, with some embryonic features. They then produce rhabdites and take up a columnar shape as they may become attached to the basal membrane. After wound setting the production of epidermal cells increases and the overcrowding of the basal membrane results in (1) detachment of stem cells and motile ciliated cells from the basal tissues, i.e. outgrowths; (2) stretching of columnar cells at the base of the outgrowths. When in the process of tissue disintegration the basal membrane of the epithelium also disappears, the cells remain in a single-layered epithelial configuration and retain their original polarity. These results are at variance with the generally accepted hypothesis that, in planarians, epidermal cells originate from the parenchyma and the epidermis is not an autonomous tissue.

Photodynamic therapy of locally advanced basal cell skin cancer

NASA Astrophysics Data System (ADS)

Riabov, Mikhail V.; Stranadko, Evgeny P.

2005-08-01

The treatment of locally spread basal-cell skin cancer is very difficult and often complicated with local recurrence. Traditional techniques are sometimes insufficient for this pathology, especially for recurrent tumors. In the State Research Center for Laser Medicine photodynamic therapy had been used for treatment of 103 patients with locally spread basal-cell skin cancer, including 64 with recurrent tumors. Therapeutic effect has been achieved in all cases, including complete tumor resorption in 67% of patients. Presented paper contains analysis of immediate and long-term follow-up results.

Neutrophil migration through preexisting holes in the basal laminae of alveolar capillaries and epithelium during streptococcal pneumonia.

PubMed

Walker, D C; Behzad, A R; Chu, F

1995-11-01

The purpose of this study was to determine whether or not there are preexisting holes in the endothelial and epithelial basal laminae of alveolar walls and to determine the path taken by neutrophils as they migrate from the capillaries to the airspace of the alveoli during inflammation. Using transmission electron microscopy and serial thin sections of normal rabbit and mouse lung, we have demonstrated the presence of slit-like holes in the capillary basal laminae and round holes in the basal laminae of type 2 pneumocytes. The slits in the capillary basal laminae were observed at the intersection of the thick and thin walls where endothelium, pericytes, and fibroblasts make close contact. The round holes in the type 2 cell basal laminae were observed at sites of close contact with fibroblasts. Neutrophils were observed to migrate through these slits and holes during streptococcal pneumonia in rabbit lungs. We conclude that during inflammation in the lung, migrating neutrophils displace pericytes and fibroblasts from the slits in the capillary basal lamina and then crawl through these slits into the alveolar interstitium. We postulate that neutrophils find their way to type 2 pneumocytes by following interstitial fibroblasts. We believe that neutrophils displace fibroblasts from their close contacts with the type 2 cells and then crawl through the holes in the basal lamina into the basal lateral space of the type 2 cells. From there, neutrophils migrate into the alveolar airspace.

Comparative study of flux of FITC-labeled Dextran 4000 on normal (iso)- and hyper-osmolarity in basal side in caco-2 cell monolayers.

PubMed

Ohkubo, Rie; Tomita, Mikio; Hotta, Yoshiyuki; Nagira, Mayuko; Hayashi, Masahiro

2003-01-01

We have shown previously that the flux of fluorescein isothiocyanate dextran 4000 (FD-4) is transported across the Caco-2 cell monolayers in a polarized fashion favoring the basal to apical direction under normal conditions (i.e., isotonic solution in basal side). Furthermore, FD-4 transport may occur via a process that included a certain degree of substrate specificity for polysaccharide and transcytosis. In the present study, we compared the flux of FD-4 in the basal to apical direction (efflux) and the apical to basal direction (influx) in stress conditions (i.e., hyperosmolarity in basal side) to those in normal conditions (i.e., iso-osmolarity in basal side). The efflux of FD-4 was increased by hyperosmolarity in basal side, but the influx was decreased when compared with normal conditions. Neither dextran 10, 000 nor colchicine inhibited the efflux of FD-4 in hyperosmolarity conditions. The inhibition of efflux of FD-4 was observed not by S-nitroso-N-acetylpenicillamine but by sodium nitroprusside and sodium ferrocyanide. These results collectively suggest that hyperosmolarity in basal side accelerates the efflux of FD-4 across the transcellular route but not across the paracellular route in Caco-2 cell monolayers. And it is indicated that cyanide rather than nitric oxide is involved in dysfunction of the FD-4 efflux system irrespective of conditions such as normal osmolarity or hyperosmolarity.

Expression of pluripotency factors in larval epithelia of the frog Xenopus: Evidence for the presence of cornea epithelial stem cells

PubMed Central

Perry, Kimberly J.; Thomas, Alvin G.; Henry, Jonathan J.

2013-01-01

Understanding the biology of somatic stem cells in self renewing tissues represents an exciting field of study, especially given the potential to harness these cells for tissue regeneration and repair in treating injury and disease. The mammalian cornea contains a population of basal epithelial stem cells involved in cornea homeostasis and repair. Research has been restricted to mammalian systems and little is known about the presence or function of these stem cells in other vertebrates. Therefore, we carried out studies to characterize frog cornea epithelium. Careful examination shows that the Xenopus larval cornea epithelium consists of three distinct layers that include an outer epithelial layer and underlying basal epithelium, in addition to a deeper fibrous layer that contains the main sensory nerve trunks that give rise to numerous branches that extend into these epithelia. These nerves convey sensory and presumably also autonomic innervation to those tissues. The sensory nerves are all derived as branches of the trigeminal nerve/ganglion similar to the situation encountered in mammals, though there appear to be some potentially interesting differences, which are detailed in this paper. We show further that numerous pluripotency genes are expressed by cells in the cornea epithelium, including: sox2, p63, various oct4 homologs, c-myc, klf4 and many others. Antibody localization revealed that p63, a well known mammalian epithelial stem cell marker, was localized strictly to all cells in the basal cornea epithelium. c-myc, was visualized in a smaller subset of basal epithelial cells and adjacent stromal tissue predominately at the periphery of the cornea (limbal zone). Finally, sox2 protein was found to be present throughout all cells of both the outer and basal epithelia, but was much more intensely expressed in a distinct subset of cells that appeared to be either multinucleate or possessed multi-lobed nuclei that are normally located at the periphery of the cornea. Using a thymidine analog (EdU), we were able to label mitotically active cells, which revealed that cell proliferation takes place throughout the cornea epithelium, predominantly in the basal epithelial layer. Species of Xenopus and one other amphibian are unique in their ability to replace a missing lens from cells derived from the basal cornea epithelium. Using EdU we show, as others have previously, that proliferating cells within the cornea epithelium do contribute to the formation of these regenerated lenses. Furthermore, using qPCR we determined that representatives of various pluripotency genes (i.e., sox2, p63 and oct60) are upregulated early during the process of lens regeneration. Antibody labeling showed that the number of sox2 expressing cells increased dramatically within 4 hours following lens removal and these cells were scattered throughout the basal layer of the cornea epithelium. Historically, the process of lens regeneration in Xenopus had been described as one involving transdifferentiation of cornea epithelial cells (i.e., one involving cellular dedifferentiation followed by redifferentiation). Our combined observations provide evidence that a population of stem cells exists within the Xenopus cornea. We hypothesize that the basal epithelium contains oligopotent epithelial stem cells that also represent the source of regenerated lenses in the frog. Future studies will be required to clearly identify the source of these lenses. PMID:23274420

Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome

PubMed Central

Arbib, Michael A.; Baldassarre, Gianluca

2017-01-01

Motor tics are a cardinal feature of Tourette syndrome and are traditionally associated with an excess of striatal dopamine in the basal ganglia. Recent evidence increasingly supports a more articulated view where cerebellum and cortex, working closely in concert with basal ganglia, are also involved in tic production. Building on such evidence, this article proposes a computational model of the basal ganglia-cerebellar-thalamo-cortical system to study how motor tics are generated in Tourette syndrome. In particular, the model: (i) reproduces the main results of recent experiments about the involvement of the basal ganglia-cerebellar-thalamo-cortical system in tic generation; (ii) suggests an explanation of the system-level mechanisms underlying motor tic production: in this respect, the model predicts that the interplay between dopaminergic signal and cortical activity contributes to triggering the tic event and that the recently discovered basal ganglia-cerebellar anatomical pathway may support the involvement of the cerebellum in tic production; (iii) furnishes predictions on the amount of tics generated when striatal dopamine increases and when the cortex is externally stimulated. These predictions could be important in identifying new brain target areas for future therapies. Finally, the model represents the first computational attempt to study the role of the recently discovered basal ganglia-cerebellar anatomical links. Studying this non-cortex-mediated basal ganglia-cerebellar interaction could radically change our perspective about how these areas interact with each other and with the cortex. Overall, the model also shows the utility of casting Tourette syndrome within a system-level perspective rather than viewing it as related to the dysfunction of a single brain area. PMID:28358814

Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome.

PubMed

Caligiore, Daniele; Mannella, Francesco; Arbib, Michael A; Baldassarre, Gianluca

2017-03-01

Motor tics are a cardinal feature of Tourette syndrome and are traditionally associated with an excess of striatal dopamine in the basal ganglia. Recent evidence increasingly supports a more articulated view where cerebellum and cortex, working closely in concert with basal ganglia, are also involved in tic production. Building on such evidence, this article proposes a computational model of the basal ganglia-cerebellar-thalamo-cortical system to study how motor tics are generated in Tourette syndrome. In particular, the model: (i) reproduces the main results of recent experiments about the involvement of the basal ganglia-cerebellar-thalamo-cortical system in tic generation; (ii) suggests an explanation of the system-level mechanisms underlying motor tic production: in this respect, the model predicts that the interplay between dopaminergic signal and cortical activity contributes to triggering the tic event and that the recently discovered basal ganglia-cerebellar anatomical pathway may support the involvement of the cerebellum in tic production; (iii) furnishes predictions on the amount of tics generated when striatal dopamine increases and when the cortex is externally stimulated. These predictions could be important in identifying new brain target areas for future therapies. Finally, the model represents the first computational attempt to study the role of the recently discovered basal ganglia-cerebellar anatomical links. Studying this non-cortex-mediated basal ganglia-cerebellar interaction could radically change our perspective about how these areas interact with each other and with the cortex. Overall, the model also shows the utility of casting Tourette syndrome within a system-level perspective rather than viewing it as related to the dysfunction of a single brain area.

Sal-like 4 (SALL4) suppresses CDH1 expression and maintains cell dispersion in basal-like breast cancer.

PubMed

Itou, Junji; Matsumoto, Yoshiaki; Yoshikawa, Kiyotsugu; Toi, Masakazu

2013-09-17

In cell cultures, the dispersed phenotype is indicative of the migratory ability. Here we characterized Sal-like 4 (SALL4) as a dispersion factor in basal-like breast cancer. Our shRNA-mediated SALL4 knockdown system and SALL4 overexpression system revealed that SALL4 suppresses the expression of adhesion gene CDH1, and positively regulates the CDH1 suppressor ZEB1. Cell behavior analyses showed that SALL4 suppresses intercellular adhesion and maintains cell motility after cell-cell interaction and cell division, which results in the dispersed phenotype. Our findings indicate that SALL4 functions to suppress CDH1 expression and to maintain cell dispersion in basal-like breast cancer. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Primary Cutaneous Carcinosarcoma of the Basal Cell Subtype Should Be Treated as a High-Risk Basal Cell Carcinoma.

PubMed

Bourgeault, Emilie; Alain, Jimmy; Gagné, Eric

2015-01-01

Cutaneous carcinosarcoma is a rare primary tumor of the skin, characterized by biphasic epithelial and mesenchymal differentiation. Due to the limited number of cases reported, there is no consensus regarding treatment and prognosis. Some authors suggest that cutaneous carcinosarcomas should be viewed as aggressive tumors, with ancillary imaging used to evaluate potential metastatic disease. Other reports demonstrate an indolent disease course, especially with epidermal-type cutaneous carcinosarcomas. We report a case of cutaneous carcinosarcoma, which we treated with electrodessication and curettage following a shave biopsy. The tumor had an epithelial component resembling a basal cell carcinoma and a fibrosarcomatous stroma. At 1-year follow-up, our patient did not show evidence of recurrence or metastasis. Our case suggests that a cutaneous carcinosarcoma with an epithelial component composed of basal cell carcinoma can be regarded as a high-risk nonmelanoma skin cancer. © The Author(s) 2015.

Basal cell adenocarcinoma of minor salivary and seromucous glands of the head and neck region.

PubMed

Fonseca, I; Soares, J

1996-05-01

Basal cell adenocarcinoma of salivary glands is an uncommon and recently described entity occurring almost exclusively at the major salivary glands. This report provides an overview of the clinicopathologic profile of this neoplasm by including the personal experience on the clinical features, microscopic and ultrastructural characteristics, proliferation activity, and DNA tumor patterns of 12 lesions occurring at the minor salivary glands of the head and neck region, where basal cell adenocarcinoma is probably an underecognized entity, previously reported under different designations. Basal cell adenocarcinoma predominates at the seventh decade without sex preference. The tumors affecting the minor salivary glands occur most frequently at the oral cavity (jugal mucosa, palate) and the upper respiratory tract. The prevalent histologic tumor pattern is represented by solid neoplastic aggregates with a peripheral cell palisading arrangement frequently delineated by basement membrane-like material. The neoplastic clusters are formed by two cell populations: the small dark cell type (that predominates) and a large cell type. Necrosis, either of the comedo or the apoptotic type, is a frequent finding. Perineural growth occurs in 50% of the cases and vascular permeation in 25%. Immunohistochemistry identifies a dual differentiation with a reactivity pattern indicative of ductal epithelial and myoepithelial differentiation, which can be confirmed by electron microscopy. The differential diagnosis of the neoplasm includes its benign counterpart, the basal cell adenoma, solid variant of adenoid cystic carcinoma, undifferentiated carcinoma, and basaloid squamous carcinoma. The tumors recur more frequently than lesions originating in major salivary glands. Mortality is associated with the anatomic site of the lesion, advanced stage, residual neoplasia at surgery, and tumor recurrence. The importance of recognizing basal cell adenocarcinoma outside major salivary glands is related to the clinical behavior of the neoplasm that seems to be less indolent than that of tumors arising in major salivary glands.

Activity of the rat osteocalcin basal promoter in osteoblastic cells is dependent upon homeodomain and CP1 binding motifs.

PubMed

Towler, D A; Bennett, C D; Rodan, G A

1994-05-01

A detailed analysis of the transcriptional machinery responsible for osteoblast-specific gene expression should provide tools useful for understanding osteoblast commitment and differentiation. We have defined three cis-elements important for basal activity of the rat osteocalcin (OC) promoter, located at about -200 to -180, -170 to -138, and -121 to -64 relative to the transcription initiation site. A motif (TCTGATTGTGT) present in the region between -200 and -170 that binds a multisubunit CP1/NFY/CBF-like CAAT factor complex contributes significantly to high level basal activity and presumably functions as the CAAT box for the rat OC promoter. We show that the region -121 to 32 is sufficient to confer osteoblastic cell type specificity in transient transfection assays of cultured cell lines using luciferase as a reporter. The basal promoter is active in rodent osteoblastic cell lines, but not in rodent fibroblastic or muscle cell lines. Although the rat OC box (-100 to -74) contains a CAAT motif, we could not detect CP1-like CAAT factor binding to this region. In fact, we demonstrate that a Msx-1 (Hox 7.1) homeodomain binding motif (ACTAATTG; bottom strand) in the 3'-end of the rat OC box is necessary for high level activity of the rat OC basal promoter in osteoblastic cells. A nuclear factor that recognizes this motif appears to be present in osteoblastic ROS 17/2.8 cells, which produce OC, but not in fibroblastic ROS 25/1 cells, which fail to express OC. This ROS 17/2.8 nuclear factor also recognizes the A/T-rich DNA cognates of the homeodomain-containing POU family of transcription factors. Taken together, these data suggest that a ubiquitous CP1-like CAAT factor and a cell type-restricted homeodomain containing (Msx or POU family) transcription factor interact with the proximal rat OC promoter to direct appropriate basal OC transcription in osteoblastic cells.

TP53 supports basal-like differentiation of mammary epithelial cells by preventing translocation of deltaNp63 into nucleoli

PubMed Central

Munne, Pauliina M.; Gu, Yuexi; Tumiati, Manuela; Gao, Ping; Koopal, Sonja; Uusivirta, Sanna; Sawicki, Janet; Wei, Gong-Hong; Kuznetsov, Sergey G.

2014-01-01

Multiple observations suggest a cell type-specific role for TP53 in mammary epithelia. We developed an in vitro assay, in which primary mouse mammary epithelial cells (mMECs) progressed from lumenal to basal-like phenotypes based on expression of Krt18 or ΔNp63, respectively. Such transition was markedly delayed in Trp53−/− mMECs suggesting that Trp53 is required for specification of the basal, but not lumenal cells. Evidence from human basal-like cell lines suggests that TP53 may support the activity of ΔNp63 by preventing its translocation from nucleoplasm into nucleoli. In human lumenal cells, activation of TP53 by inhibiting MDM2 or BRCA1 restored the nucleoplasmic expression of ΔNp63. Trp53−/− mMECs eventually lost epithelial features resulting in upregulation of MDM2 and translocation of ΔNp63 into nucleoli. We propose that TP63 may contribute to TP53-mediated oncogenic transformation of epithelial cells and shed light on tissue- and cell type-specific biases observed for TP53-related cancers. PMID:24722541

Ascl1 (Mash1) Knockout Perturbs Differentiation of Nonneuronal Cells in Olfactory Epithelium

PubMed Central

Jang, Woochan; Wildner, Hendrik; Schwob, James E.

2012-01-01

The embryonic olfactory epithelium (OE) generates only a very few olfactory sensory neurons when the basic helix-loop-helix transcription factor, ASCL1 (previously known as MASH1) is eliminated by gene mutation. We have closely examined the structure and composition of the OE of knockout mice and found that the absence of neurons dramatically affects the differentiation of multiple other epithelial cell types as well. The most prominent effect is observed within the two known populations of stem and progenitor cells of the epithelium. The emergence of horizontal basal cells, a multipotent progenitor population in the adult epithelium, is anomalous in the Ascl1 knockout mice. The differentiation of globose basal cells, another multipotent progenitor population in the adult OE, is also aberrant. All of the persisting globose basal cells are marked by SOX2 expression, suggesting a prominent role for SOX2 in progenitors upstream of Ascl1. However, NOTCH1-expressing basal cells are absent from the knockout; since NOTCH1 signaling normally acts to suppress Ascl1 via HES1 and drives sustentacular (Sus) cell differentiation during adult epithelial regeneration, its absence suggests reciprocity between neurogenesis and the differentiation of Sus cells. Indeed, the Sus cells of the mutant mice express a markedly lower level of HES1, strengthening that notion of reciprocity. Duct/gland development appears normal. Finally, the expression of cKIT by basal cells is also undetectable, except in those small patches where neurogenesis escapes the effects of Ascl1 knockout and neurons are born. Thus, persistent neurogenic failure distorts the differentiation of multiple other cell types in the olfactory epithelium. PMID:23284756

Multidimensional Single Cell Based STAT Phosphorylation Profiling Identifies a Novel Biosignature for Evaluation of Systemic Lupus Erythematosus Activity

PubMed Central

Huang, Xinfang; Guo, Yanzhi; Bao, Chunde; Shen, Nan

2011-01-01

Introduction Dysregulated cytokine action on immune cells plays an important role in the initiation and progress of systemic lupus erythematosus (SLE), a complex autoimmune disease. Comprehensively quantifying basal STATs phosphorylation and their signaling response to cytokines should help us to better understand the etiology of SLE. Methods Phospho-specific flow cytometry was used to measure the basal STAT signaling activation in three immune cell types of peripheral-blood mononuclear cells from 20 lupus patients, 9 rheumatoid arthritis (RA) patients and 13 healthy donors (HDs). A panel of 27 cytokines, including inflammatory cytokines, was measured with Bio-Plex™ Human Cytokine Assays. Serum Prolactin levels were measured with an immunoradiometric assay. STAT signaling responses to inflammatory cytokines (interferon α [IFNα], IFNγ, interleukin 2 [IL2], IL6, and IL10) were also monitored. Results We observed the basal activation of STAT3 in SLE T cells and monocytes, and the basal activation of STAT5 in SLE T cells and B cells. The SLE samples clustered into two main groups, which were associated with the SLE Disease Activity Index 2000, their erythrocyte sedimentation rate, and their hydroxychloroquine use. The phosphorylation of STAT5 in B cells was associated with cytokines IL2, granulocyte colony-stimulating factor (G-CSF), and IFNγ, whereas serum prolactin affected STAT5 activation in T cells. The responses of STAT1, STAT3, and STAT5 to IFNα were greatly reduced in SLE T cells, B cells, and monocytes, except for the STAT1 response to IFNα in monocytes. The response of STAT3 to IL6 was reduced in SLE T cells. Conclusions The basal activation of STATs signaling and reduced response to cytokines may be helpful us to identify the activity and severity of SLE. PMID:21799742

Improved Chemically Defined Basal Medium (CMRL-1969) for Primary Monkey Kidney and Human Diploid Cells 1

PubMed Central

Healy, G. M.; Teleki, S.; Seefried, A. V.; Walton, M. J.; Macmorine, H. G.

1971-01-01

An improved tissue culture basal medium, CMRL-1969, supplemented with serum, has been evaluated by measuring the growth responses of primary cultures of trypsin-dispersed monkey kidney cells (PMKC) and of an established culture of a human diploid cell strain (HDCS). Medium H597, an early modification of medium 199 which has been used successfully in the preparation of poliomyelitis vaccine for 15 years, was used for comparison. In addition, parallel testing was done with Basal Medium Eagle (BME) widely used for the growth of HDCS. The improvements in basal medium CMRL-1969 are attributed to changes in amino acid concentrations, in vitamin composition, and, in particular, to enhanced buffering capacity. The latter has been achieved by the use of free-base amino acids and by increasing the dibasic sodium phosphate. The new medium has already been used to advantage for the production of polioviruses in PMKC where equivalent titers were obtained from cultures initiated with 70% of the number of cells required with earlier media. The population-doubling time was reduced in this system. Also, with small inocula of HDCS, the time required to obtain maximum cell yield was shorter with CMRL-1969 than with BME. Both media were supplemented with 10% calf serum. Maximum cell yields after repeated subcultivation in the new basal medium were greatly increased and the stability of the strain, as shown by chromosomal analysis, was not affected. Basal medium CMRL-1969 can be prepared easily in liquid or powdered form. PMID:4322279

Relation of biomass to basal area and site index on an Appalachian watershed

Treesearch

Harry V., Jr. Wiant; Robert Knight; John E. Baumgras

1984-01-01

The biomass of 50-year-old cove hardwood and upland oak stands on an Appalachian watershed was more strongly related to basal area than to site index. Equations are presented for predicting the green and dry weight per acre of biomass components with basal area as the independent variable.

For Some Skin Cancers, Targeted Drug Hits the Mark

Cancer.gov

Two studies reported June 7, 2012, in NEJM indicate that the drug vismodegib can elicit responses in people with advanced or metastatic basal cell carcinoma and help shrink or prevent tumors in those with basal cell nevus syndrome.

Quantitative fluorescence in situ hybridization measurement of telomere length in skin with/without sun exposure or actinic keratosis.

PubMed

Ikeda, Hiroyuki; Aida, Junko; Hatamochi, Atsushi; Hamasaki, Yoichiro; Izumiyama-Shimomura, Naotaka; Nakamura, Ken-Ichi; Ishikawa, Naoshi; Poon, Steven S; Fujiwara, Mutsunori; Tomita, Ken-Ichiro; Hiraishi, Naoki; Kuroiwa, Mie; Matsuura, Masaaki; Sanada, Yukihiro; Kawano, Youichi; Arai, Tomio; Takubo, Kaiyo

2014-03-01

Chromosomal and genomic instability due to telomere dysfunction is known to play an important role in carcinogenesis. To study telomere shortening in the epidermis surrounding actinic keratosis, we measured telomere lengths of basal, parabasal, and suprabasal cells in epidermis with actinic keratosis (actinic keratosis group, n = 18) and without actinic keratosis (sun-protected, n = 15, and sun-exposed, n = 13 groups) and in actinic keratosis itself as well as in dermal fibroblasts in the 3 groups, using quantitative fluorescence in situ hybridization. Among the 3 cell types, telomeres of basal cells were not always the longest, suggesting that tissue stem cells are not necessarily located among basal cells. Telomeres of basal cells in the sun-exposed group were shorter than those in the sun-protected group. Telomeres in the background of actinic keratosis and in actinic keratosis itself and those of fibroblasts in actinic keratosis were significantly shorter than those in the controls. Our findings demonstrate that sun exposure induces telomere shortening and that actinic keratosis arises from epidermis with shorter telomeres despite the absence of any histologic atypia. © 2014.

PGE2 /EP4 Signaling Controls the Transfer of the Mammary Stem Cell State by Lipid Rafts in Extracellular Vesicles.

PubMed

Lin, Meng-Chieh; Chen, Shih-Yin; Tsai, Ho-Min; He, Pei-Lin; Lin, Yen-Chun; Herschman, Harvey; Li, Hua-Jung

2017-02-01

Prostaglandin E 2 (PGE 2 )-initiated signaling contributes to stem cell homeostasis and regeneration. However, it is unclear how PGE 2 signaling controls cell stemness. This study identifies a previously unknown mechanism by which PGE 2 /prostaglandin E receptor 4 (EP 4 ) signaling regulates multiple signaling pathways (e.g., PI3K/Akt signaling, TGFβ signaling, Wnt signaling, EGFR signaling) which maintain the basal mammary stem cell phenotype. A shift of basal mammary epithelial stem cells (MaSCs) from a mesenchymal/stem cell state to a non-basal-MaSC state occurs in response to prostaglandin E receptor 4 (EP 4 ) antagonism. EP 4 antagonists elicit release of signaling components, by controlling their trafficking into extracellular vesicles/exosomes in a lipid raft/caveolae-dependent manner. Consequently, EP 4 antagonism indirectly inactivates, through induced extracellular vesicle/exosome release, pathways required for mammary epithelial stem cell homeostasis, e.g. canonical/noncanonical Wnt, TGFβ and PI3K/Akt pathways. EP 4 antagonism causes signaling receptors and signaling components to shift from non-lipid raft fractions to lipid raft fractions, and to then be released in EP 4 antagonist-induced extracellular vesicles/exosomes, resulting in the loss of the stem cell state by mammary epithelial stem cells. In contrast, luminal mammary epithelial cells can acquire basal stem cell properties following ingestion of EP 4 antagonist-induced stem cell extracellular vesicles/exosomes, and can then form mammary glands. These findings demonstrate that PGE 2 /EP 4 signaling controls homeostasis of mammary epithelial stem cells through regulating extracellular vesicle/exosome release. Reprogramming of mammary epithelial cells can result from EP 4 -mediated stem cell property transfer by extracellular vesicles/exosomes containing caveolae-associated proteins, between mammary basal and luminal epithelial cells. Stem Cells 2017;35:425-444. © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Predicting round window niche visibility via the facial recess using high-resolution computed tomography.

PubMed

Kashio, Akinori; Sakamoto, Takashi; Karino, Shotaro; Kakigi, Akinobu; Iwasaki, Shinichi; Yamasoba, Tatsuya

2015-01-01

To predict round window niche (RWN) visibility using high-resolution computed tomography (HRCT). Case series with chart review. Academic tertiary care center. We retrospectively reviewed 70 cochlear implant ears that underwent presurgical axial HRCT with a surgical video recorder. The visibility of the RWN was classified into three types: 17 as invisible or nearly invisible, 22 as partially visible, and 31 as fully visible. Next, we measured the following three radiologic parameters: 1) the angle of the external auditory canal (EAC) relative to the cochlear basal turn, 2) the width of the facial recess, and 3) the relative location of the facial nerve (FN) to the cochlear basal turn. These were compared with the RWN visibility. Subsequently, to predict the RWN visibility, a line was created parallel to the EAC line and along the anterior lateral FN. The location of the line relative to the round window membrane was compared with the RWN view. In cases that had poor RWN visibility, the angle of the posterior canal wall portion of the EAC relative to the cochlear basal turn was significantly smaller and the location of the FN to the cochlear basal turn was closer. The location of the prediction line to the round window membrane highly predicted the RWN view during the surgery. The RWN visibility and the preoperative HRCT findings showed a high correlation. Drawing the prediction line is a simple and useful way for preoperatively predicting the RWN visibility in cochlear implant surgery.

New data about the suspensor of succulent angiosperms: Ultrastructure and cytochemical study of the embryo-suspensor of Sempervivum arachnoideum L. and Jovibarba sobolifera (Sims) Opiz.

PubMed

Kozieradzka-Kiszkurno, Małgorzata; Płachno, Bartosz Jan; Bohdanowicz, Jerzy

2012-07-01

The development of the suspensor in two species - Sempervivum arachnoideum and Jovibarba sobolifera - was investigated using cytochemical methods, light and electron microscopy. Cytological processes of differentiation in the embryo-suspensor were compared with the development of embryo-proper. The mature differentiated suspensor consists of a large basal cell and three to four chalazal cells. The basal cell produces haustorial branched invading ovular tissues. The walls of the haustorium and the micropylar part of the basal cell form the wall ingrowths typical for a transfer cells. The ingrowths also partially cover the lateral wall and the chalazal wall separating the basal cell from the other embryo cells. The dense cytoplasm filling the basal cell is rich in: numerous polysomes lying free or covering rough endoplasmic reticulum (RER), active dictyosomes, microtubules, bundles of microfilaments, microbodies, mitochondria, plastids and lipid droplets. Cytochemical tests (including proteins, insoluble polysaccharides and lipids are distributed in the suspensor during different stages of embryo development) showed the presence of high amounts of macromolecules in the suspensor cells, particularly during the globular and heart-shaped phases of embryo development. The protein bodies and lipid droplets are the main storage products in the cells of the embryo-proper. The results of Auramine 0 indicate that a cuticular material is present only on the surface walls of the embryo-proper, but is absent from the suspensor cell wall. The ultrastructural features and cytochemical tests indicate that in the two species - S. arachnoideum and J. sobolifera - the embryo-suspensor is mainly involved in the absorption and transport of metabolites from the ovular tissues to the developing embryo-proper.

The incidence of satellite cysts in keratocystic odontogenic tumors.

PubMed

Pavelić, Boiidar; Katunarić, Marina; Segović, Sanja; Karadole, Maja Cimas; Katanec, Davor; Saban, Aida; Puhar, Ivan

2014-03-01

Renaming of the Odontogenic Keratocyst as the Keratocystic Odontogenic Tumor by the World Health Organization (WHO) is based on the aggressive nature of this lesion. Satellite cysts founded in the walls of the original cysts may give rise to a new lesion formation. The aim of this retrospecitve study was to identify the existence of specific features according incidence of satellite cysts and the pallisading of the basal layer of the epithelium and to establish their mutual correlation. The histopathologic data of Keratocystic Odontogenic Tumor on the basis of new WHO's classification (2005) were analized. Prominent palisade basal cell layer was found in 415 (94.75%) and partially absent palisade basal cell layer in 23 (5.25%) cases. Satellite cysts were presented in prominent palisade basal cell layer in 85 specimens (20.5%) and in cases with partial absent of the palisade basal layer in 3 spicemens (13%). The higher the frequency of pallisading was the higher the frequency of satellite cysts was (p > 0.05).

Trastuzumab-Resistant Luminal B Breast Cancer Cells Show Basal-Like Cell Growth Features Through NF-κB-Activation

PubMed Central

Kanzaki, Hirotaka; Mukhopadhya, Nishit K.; Cui, Xiaojiang; Ramanujan, V. Krishnan

2016-01-01

A major clinical problem in the treatment of breast cancer is mortality due to metastasis. Understanding the molecular mechanisms associated with metastasis should aid in designing new therapeutic approaches for breast cancer. Trastuzumab is the main therapeutic option for HER2+ breast cancer patients; however, the molecular basis for trastuzumab resistance (TZR) and subsequent metastasis is not known. Earlier, we found expression of basal-like molecular markers in TZR tissues from patients with invasive breast cancer.(1) The basal-like phenotype is a particularly aggressive form of breast cancer. This observation suggests that TZR might contribute to an aggressive phenotype. To understand if resistance to TZR can lead to basal-like phenotype, we generated a trastuzumab-resistant human breast cancer cell line (BT-474-R) that maintained human epidermal growth factor receptor 2 (HER2) overexpression and HER2 mediated signaling. Analysis showed that nuclear factor-kappa B (NF-κB) was constitutively activated in the BT-474-R cells, a feature similar to the basal-like tumor phenotype. Pharmacologic inhibition of NF-κB improved sensitivity of BT-474-R cells to trastuzumab. Interestingly, activation of HER2 independent NF-κB is not shown in luminal B breast cancer cells. Our study suggests that by activating the NF-κB pathway, luminal B cells may acquire a HER2+ basal-like phenotype in which NF-κB is constitutively activated; this notion is consistent with the recently proposed “progression through grade” or “evolution of resistance” hypothesis. Furthermore, we identified IKK-α/IKK-β and nuclear accumulation of RelA/p65 as the major determinants in the resistant cells. Thus our study additionally suggests that the nuclear accumulation of p65 may be a useful marker for identifying metastasis-initiating tumor cells and targeting RelA/p65 may limit metastasis of breast and other cancers associated with NF-κB activation. PMID:26871511

Growth and Yield of Appalachian Mixed Hardwoods After Thinning

Treesearch

Wade C. Harrison; Harold E. Burkhart; Thomas E. Burk; Donald E. Beckand

1986-01-01

G-RAT (Growth of Hardwoods After Thinning) is a system of computer programs used to predict growth and yield of Appalachian mixed hardwoods after thinning. Given a tree list or stand table, along with inputs of stand age, site index, and stand basal area before thinning, G-RAT software uses species-specific individual tree equations to predict tree basal area...

Heat shock protein-27 protects human bronchial epithelial cells against oxidative stress–mediated apoptosis: possible implication in asthma

PubMed Central

Merendino, Anna M.; Paul, Catherine; Vignola, Antonio M.; Costa, Maria A.; Melis, Mario; Chiappara, Giuseppina; Izzo, V.; Bousquet, J.; Arrigo, André-Patrick

2002-01-01

Inflammation of the human bronchial epithelium, as observed in asthmatics, is characterized by the selective death of the columnar epithelial cells, which desquamate from the basal cells. Tissue repair initiates from basal cells that resist inflammation. Here, we have evaluated the extent of apoptosis as well as the Hsp27 level of expression in epithelial cells from bronchial biopsy samples taken from normal and asthmatic subjects. Hsp27 is a chaperone whose expression protects against oxidative stress. We report that in asthmatic subjects the basal epithelium cells express a high level of Hsp27 but no apoptotic morphology. In contrast, apoptotic columnar cells are devoid of Hsp27 expression. Moreover, we observed a decreased resistance to hydrogen peroxide–induced apoptosis in human bronchial epithelial 16–HBE cells when they were genetically modified to express reduced levels of Hsp27. PMID:12482203

1,1-Bis(3'-indolyl)-1-(p-biphenyl)methane inhibits basal-like breast cancer growth in athymic nude mice

PubMed Central

Su, Yunpeng; Vanderlaag, Kathryn; Ireland, Courtney; Ortiz, Janelle; Grage, Henry; Safe, Stephen; Frankel, Arthur E

2007-01-01

Introduction 1,1-Bis (3'-indolyl)-1-(p-biphenyl) methane (CDIM9) has been identified as a new peroxisome proliferator-activated receptor (PPAR)-γ agonist that exhibits both receptor dependent and independent antitumor activities. CDIM9 has not previously been studied with respect to its effects against basal-like breast cancer. Our goal in the present study was to investigate the anti-basal-like breast tumor activity of CDIM9 in vitro and in vivo. Methods The effects of CDIM9 on cell protein and DNA syntheses were determined in basal-like breast cancer MDA-MB231 and BT549 cells in vitro. Maximum tolerated dose and dose-limited toxicity were determined in BalB/c mice, and antitumor growth activities were assessed in MDA-MB231 basal-like breast tumor xenografts in athymic nude mice. Results CDIM9 exhibited selective cell cytotoxicity and anti-proliferation effects on basal-like breast cancer lines. In MDA-MB231 cell, CDIM9 induced caveolin-1 and p27 expression, which was significantly downregulated by co-treatment with the PPAR-γ antagonist GW9662. Nonsteroidal anti-inflammatory drug-activated gene-1 and activating transcription factor-3 were upregulated by CDIM9 through a PPAR-γ independent pathway. CDIM9 (40 mg/kg daily, intraperitoneally, for 35 days) inhibited the growth of subcutaneous MDA-MB231 tumor xenografts by 87%, and produced a corresponding decrease in proliferation index. Nearly half of the treated mice (46%) had complete durable remissions, confirmed by histology. The growth of an established tumor was inhibited by CDIM9 treatment (64 mg/kg daily, intraperitoneally, for 10 days), with a mean tumor growth inhibition of 67% as compared with controls. CDIM9 induced increases in tumor caveolin-1 and p27 in vivo, which may contribute to its antitumor activity in basal-like breast cancer. Conclusion CDIM9 showed potent antiproliferative effects on basal-like breast cancer cell in tissue culture and dramatic growth inhibition in animal models at safe doses. These findings justify further development of this drug for treatment of basal-like breast cancer. PMID:17764562

Syndrome in question: Gorlin-Goltz syndrome.

PubMed

Ribeiro, Pauline Lyrio; Souza, João Basílio de; Abreu, Karina Demoner de; Brezinscki, Marisa Simon; Pignaton, Christine Chambo

2016-01-01

The Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is an uncommon disorder caused by a mutation in Patched, tumor suppressor gene. It is mainly characterized by numerous early onset basal cell carcinomas, odontogenic cysts of jaw and skeletal abnormalities. Due to the wide clinical spectrum, treatment and management of its modalities are not standardized and should be individualized and monitored by a multidisciplinary team. We report a typical case in a 30-year-old man with multiple basal cell carcinomas, keratotic pits of palmar creases and bifid ribs, with a history of several corrective surgeries for keratocystic odontogenic tumors, among other lesions characteristic of the syndrome.

Basal Cell Carcinoma: A Patient and Physician's Experience.

PubMed

Cohen, Barbara J; Cohen, Eliahou S; Cohen, Philip R

2018-06-02

In this article, the first coauthor, a patient with a basal cell carcinoma on her upper lip, discusses her experience with Mohs micrographic surgery for the treatment of the skin cancer. The second coauthor, who is the patient's physician (a dermatologist who shares her last name but is not a relative), diagnosed her skin cancer and referred her for Mohs surgery. The third coauthor, who is the patient's son and not only a dermatologist, but also a dermatopathologist and a Mohs surgeon (and also shares her last name), summarizes the presentation and treatment of the basal cell carcinoma.

Basal cell carcinoma of the skin (part 1): epidemiology, pathology and genetic syndromes.

PubMed

Correia de Sá, Tiago Ribeiro; Silva, Roberto; Lopes, José Manuel

2015-11-01

Basal cell carcinoma (BCC) is the most common skin cancer worldwide with increasing incidence, but difficult to assess due to the current under registration practice. Despite the low mortality rate, BCC is a cause of great morbidity and an economic burden to health services. There are several risk factors that increase the risk of BCC and partly explain its incidence. Low-penetrance susceptibility alleles, as well as genetic alterations in signaling pathways, namely SHH pathway, also contribute to the carcinogenesis. BCC associate with several genetic syndromes, of which basal cell nevus syndrome is the most common.

Multispectral imaging system based on light-emitting diodes for the detection of melanomas and basal cell carcinomas: a pilot study

NASA Astrophysics Data System (ADS)

Delpueyo, Xana; Vilaseca, Meritxell; Royo, Santiago; Ares, Miguel; Rey-Barroso, Laura; Sanabria, Ferran; Puig, Susana; Pellacani, Giovanni; Noguero, Fernando; Solomita, Giuseppe; Bosch, Thierry

2017-06-01

This article proposes a multispectral system that uses the analysis of the spatial distribution of color and spectral features to improve the detection of skin cancer lesions, specifically melanomas and basal cell carcinomas. The system consists of a digital camera and light-emitting diodes of eight different wavelengths (414 to 995 nm). The parameters based on spectral features of the lesions such as reflectance and color, as well as others empirically computed using reflectance values, were calculated pixel-by-pixel from the images obtained. Statistical descriptors were calculated for every segmented lesion [mean (x˜), standard deviation (σ), minimum, and maximum]; descriptors based on the first-order statistics of the histogram [entropy (Ep), energy (En), and third central moment (μ3)] were also obtained. The study analyzed 429 pigmented and nonpigmented lesions: 290 nevi and 139 malignant (95 melanomas and 44 basal cell carcinomas), which were split into training and validation sets. Fifteen parameters were found to provide the best sensitivity (87.2% melanomas and 100% basal cell carcinomas) and specificity (54.5%). The results suggest that the extraction of textural information can contribute to the diagnosis of melanomas and basal cell carcinomas as a supporting tool to dermoscopy and confocal microscopy.

Sulfur mustard-induced apoptosis in hairless guinea pig skin.

PubMed

Kan, Robert K; Pleva, Christina M; Hamilton, Tracey A; Anderson, Dana R; Petrali, John P

2003-01-01

The present study was aimed to examine whether apoptosis is involved in the pathogenesis of sulfur mustard (SM)-induced basal cell death. Skin sites of the hairless guinea pig exposed to SM vapor for 8 minutes were harvested at 3, 6, 12, 24, and 48 hours postexposure. Immunohistochemical detection of basal cell apoptosis was performed using the ApopTag in situ apoptosis labeling kit. Only occasional apoptotic basal cells (BC)were observed in nonexposed and perilesional control sites. At lesional sites, apoptosis of BC was not detected at 3 hours postexposure. However, at 6 hours and 12 hours postexposure, 18% and 59% of BC were apoptotic, respectively. At 24 and 48 hours postexposure, individual apoptotic basal cells were not clearly recognizable due to necrosis. At the ultrastructural level, degenerating BC exhibited typical apoptotic morphology including nuclear condensation and chromatin margination. The results suggest that apoptotic cell death is a cytotoxic mechanism with the number of BC undergoing apoptosis significantly increasing from 6 to 12 hours postexposure. In addition, because necrosis is preferential at 24 hours postexposure, we believe that SM-induced cell death involves early apoptosis and late necrosis, which temporally overlap to produce a single cell death pathway along an apoptotic-necrotic continuum.

A Case of Metastatic Basal Cell Carcinoma Treated with Cisplatin and Adriamycin.

PubMed

Kanzaki, Akiko; Ansai, Shin-Ichi; Ueno, Takashi; Kawana, Seiji; Shimizu, Akira; Naito, Zenya; Saeki, Hidehisa

2017-01-01

A 72-year-old man was referred to our hospital for treatment of an ulcer that had been growing on his back for 10 years. Physical examination showed an ulcerated tumor from the neck to the back and swollen cervical lymph nodes. The tumor size was 12×9 cm. Histology of the biopsy showed a nodular and morpheic basal cell carcinoma (BCC). A chest computed tomography (CT) scan showed multiple lung tumors. CT-guided biopsy of the lung and the cervical lymph node revealed metastatic basal cell carcinoma (MBCC). The primary skin tumor was resected and a total of 10 courses of cisplatin (25 mg/m 2 /day×75%) and adriamycin (50 mg/m 2 ×75%) were administered for metastatic basal cell carcinoma (MBCC). The patient died 5 years and 3 months after his first visit. Autopsy revealed MBCC in the lung, kidney, pancreas, several lymph nodes, liver and bone. A portion of the tumor cells were composed of squamoid cells with eosinophilic cytoplasm, large nuclei, lack of the characteristic peripheral palisading and retraction artifacts, and variable cytoplasmic keratinization. These pathological findings were compatible with basosquamous cell carcinoma. Chemotherapy was effective for MBCC in this patient.

Elucidating the Tumor Suppressive Role of SLITs in Maintaining the Basal Cell Niche

DTIC Science & Technology

2009-07-01

deregulated upon cancerous transformation. 15. SUBJECT TERMS breast , Slit2, Robo1, basal cell 16. SECURITY CLASSIFICATION OF: 17. LIMITATION...natural
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A Novel Nectin-mediated Cell Adhesion Apparatus That Is Implicated in Prolactin Receptor Signaling for Mammary Gland Development*

PubMed Central

Kitayama, Midori; Mizutani, Kiyohito; Maruoka, Masahiro; Mandai, Kenji; Sakakibara, Shotaro; Ueda, Yuki; Komori, Takahide; Shimono, Yohei; Takai, Yoshimi

2016-01-01

Mammary gland development is induced by the actions of various hormones to form a structure consisting of collecting ducts and milk-secreting alveoli, which comprise two types of epithelial cells known as luminal and basal cells. These cells adhere to each other by cell adhesion apparatuses whose roles in hormone-dependent mammary gland development remain largely unknown. Here we identified a novel cell adhesion apparatus at the boundary between the luminal and basal cells in addition to desmosomes. This apparatus was formed by the trans-interaction between the cell adhesion molecules nectin-4 and nectin-1, which were expressed in the luminal and basal cells, respectively. Nectin-4 of this apparatus further cis-interacted with the prolactin receptor in the luminal cells to enhance the prolactin-induced prolactin receptor signaling for alveolar development with lactogenic differentiation. Thus, a novel nectin-mediated cell adhesion apparatus regulates the prolactin receptor signaling for mammary gland development. PMID:26757815

The number of multinucleated trophoblastic giant cells in the basal decidua is decreased in retained placenta.

PubMed

van Beekhuizen, H J; Joosten, I; de Groot, A N J A; Lotgering, F K; van der Laak, J; Bulten, J

2009-09-01

Retained placenta (RP) is a major cause of obstetric haemorrhage. The aim of the study was to obtain a better understanding of the mechanisms that cause some placentas to become retained, while most are not. 23 RPs clinically diagnosed as placenta adhesiva and 10 control placentas (CPs) were examined for differences in trophoblast fusion into multinucleated trophoblastic giant cells (MTGCs), defects in the basal decidua, and decidual attachment of myometrial fibres. The number of MTGCs in the basal decidua was significantly smaller in RPs (0.23 MTGC/standard length) than in CPs (1.11 MTGC/standard length) (p<0.001). Defects in the decidua were observed in 4% of the RPs and in 0% of the CPs. Myometrial fibres were attached to the decidua in 78% of the RPs and in 0% of the CPs (p<0.001). In placenta adhesiva compared with CPs, significantly less MTGCs were present in the basal decidua, the basal decidua was intact, and myometrial fibres were more frequently attached to the basal decidua. It is speculated that these findings may indicate that defective fusion of trophoblastic cells into MTGCs plays a causative role in placenta adhesiva.

Synergistic actions of pemphigus vulgaris IgG, Fas-ligand and tumor necrosis factor-alpha during induction of basal cell shrinkage and acantholysis.

PubMed

Orlov, Maxim D; Chernyavsky, Alex I; Arredondo, Juan; Grando, Sergei A

2006-11-01

This study tested a recently proposed "Basal Cell Shrinkage" hypothesis of pemphigus acantholysis through a quantitative analysis of individual and cooperative effects of pemphigus vulgaris (PV) IgG, Fas-ligand (Fas-L) and tumor necrosis factor-alpha (TNFalpha) on keratinocyte (KC) volume (i.e. cell size) and adhesive properties. Exposure of KC monolayers and MatTek EpiDermFT tissues cultures to the physiologic concentrations of Fas-L, TNFalpha or IgGs from two PV patients resulted in various degrees of reversible changes, which were not observed in control cultures either exposed to normal IgG or left intact. Within 12-24 h of exposure, basal cells in experimental cultures lost their ability to form stress fibers, retracted cytoplasmic aprons and formed keratin aggregates, indicating that their cytoskeleton collapsed. The cell volume decreased significantly (p < 0.05) as the polygonal cell shape changed to a round one. The shrunk cells detached from their neighbors and the substrate, resulting in a reciprocal increase of both the areas of acantholysis and the number of detached KCs, respectively. Since in the skin of PV patients, KCs are targeted by autoantibodies concomitantly with being exposed to autocrine and paracrine pro-apoptotic and pro-inflammatory cytokines, we combined PV IgG with Fas-L and/or TNFalpha in the cell culture experiments. This amplified several fold an ability of PV IgG to cause basal cell shrinkage and detachment. The obtained results demonstrated for the first time that PV IgG works together with Fas-L and TNFalpha to induce acantholysis via basal cell shrinkage, which provides a novel mechanism explaining successful treatment of PV patients with TNFalpha inhibitors.

LIPG signaling promotes tumor initiation and metastasis of human basal-like triple-negative breast cancer

PubMed Central

Lo, Pang-Kuo; Yao, Yuan; Lee, Ji Shin; Zhang, Yongshu; Huang, Weiliang; Kane, Maureen A

2018-01-01

Current understanding of aggressive human basal-like triple-negative breast cancer (TNBC) remains incomplete. In this study, we show endothelial lipase (LIPG) is aberrantly overexpressed in basal-like TNBCs. We demonstrate that LIPG is required for in vivo tumorigenicity and metastasis of TNBC cells. LIPG possesses a lipase-dependent function that supports cancer cell proliferation and a lipase-independent function that promotes invasiveness, stemness and basal/epithelial-mesenchymal transition features of TNBC. Mechanistically, LIPG executes its oncogenic function through its involvement in interferon-related DTX3L-ISG15 signaling, which regulates protein function and stability by ISGylation. We show that DTX3L, an E3-ubiquitin ligase, is required for maintaining LIPG protein levels in TNBC cells by inhibiting proteasome-mediated LIPG degradation. Inactivation of LIPG impairs DTX3L-ISG15 signaling, indicating the existence of DTX3L-LIPG-ISG15 signaling. We further reveal LIPG-ISG15 signaling is lipase-independent. We demonstrate that DTX3L-LIPG-ISG15 signaling is essential for malignancies of TNBC cells. Targeting this pathway provides a novel strategy for basal-like TNBC therapy. PMID:29350614

Increase of poorly proliferated p63+ /Ki67+ basal cells forming multiple layers in the aberrant remodeled epithelium in nasal polyps.

PubMed

Zhao, L; Li, Y Y; Li, C W; Chao, S S; Liu, J; Nam, H N; Dung, N T N; Shi, L; Wang, D Y

2017-06-01

Aberrant epithelial remodeling with the ectopic expression of p63 (basal cell markers) is an important pathologic phenomenon seen in chronically inflamed airway epithelium such as in nasal polyps (NPs). Biopsies were obtained from 55 NP patients and 18 healthy controls (inferior turbinate). Among NP patients, 15 were treated with oral and nasal steroids, so that two sets of NP biopsies were taken before and after the treatments. p63, Ki67, type IV β-tubulin, and cell cycle markers were investigated in these specimens. The number of p63 + cells is significantly higher in both hyperplastic (1.53-fold, P < 0.0001) and squamous metaplastic (2.02-fold, P < 0.0001) epithelium from NPs than from healthy controls. There are three types of proliferative basal cells (p63 + /Ki67 + ) which are in different phases of the cell cycle, such as G1 phase (type I cells), S to G2 phase (type II cells), and mitosis (type III cells). Of importance, some type I cells may arrest after proliferation although they may still be p63 + /Ki67 + . In healthy epithelium, the ratio of the type I and II cells is almost 50:50. However, less type II cells are found in hyperplastic epithelium (34.85%, P = 0.012) and in squamous metaplastic epithelium (30.77%, P = 0.02) together with the presence of type III cells (3.45%, P = 0.01). These findings were not changed after steroid treatments. An increase of poorly proliferated basal cells forming multiple layers, which may stain for basal cell markers but does not form a proper epidermal barrier, is an important histopathologic phenomenon in aberrant remodeled epithelium of NPs. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Synaptic plasticity in a cerebellum-like structure depends on temporal order

NASA Astrophysics Data System (ADS)

Bell, Curtis C.; Han, Victor Z.; Sugawara, Yoshiko; Grant, Kirsty

1997-05-01

Cerebellum-like structures in fish appear to act as adaptive sensory processors, in which learned predictions about sensory input are generated and subtracted from actual sensory input, allowing unpredicted inputs to stand out1-3. Pairing sensory input with centrally originating predictive signals, such as corollary discharge signals linked to motor commands, results in neural responses to the predictive signals alone that are Negative images' of the previously paired sensory responses. Adding these 'negative images' to actual sensory inputs minimizes the neural response to predictable sensory features. At the cellular level, sensory input is relayed to the basal region of Purkinje-like cells, whereas predictive signals are relayed by parallel fibres to the apical dendrites of the same cells4. The generation of negative images could be explained by plasticity at parallel fibre synapses5-7. We show here that such plasticity exists in the electrosensory lobe of mormyrid electric fish and that it has the necessary properties for such a model: it is reversible, anti-hebbian (excitatory postsynaptic potentials (EPSPs) are depressed after pairing with a postsynaptic spike) and tightly dependent on the sequence of pre- and postsynaptic events, with depression occurring only if the postsynaptic spike follows EPSP onset within 60 ms.

Cellular origin of bladder neoplasia and tissue dynamics of its progression to invasive carcinoma

PubMed Central

Shin, Kunyoo; Lim, Agnes; Odegaard, Justin I.; Honeycutt, Jared D.; Kawano, Sally; Hsieh, Michael H.; Beachy, Philip A.

2014-01-01

Understanding how malignancies arise within normal tissues requires identification of the cancer cell of origin and knowledge of the cellular and tissue dynamics of tumor progression. Here we examine bladder cancer in a chemical carcinogenesis model that mimics muscle-invasive human bladder cancer. With no prior bias regarding genetic pathways or cell types, we prospectively mark or ablate cells to show that muscle-invasive bladder carcinomas arise exclusively from Sonic hedgehog (Shh)-expressing stem cells in basal urothelium. These carcinomas arise clonally from a single cell whose progeny aggressively colonize a major portion of the urothelium to generate a lesion with histological features identical to human carcinoma-in-situ. Shh-expressing basal cells within this precursor lesion become tumor-initiating cells, although Shh expression is lost in subsequent carcinomas. We thus find that invasive carcinoma is initiated from basal urothelial stem cells but that tumor cell phenotype can diverge significantly from that of the cancer cell-of-origin. PMID:24747439

Infection of Polarized MDCK Cells with Herpes Simplex Virus 1: Two Asymmetrically Distributed Cell Receptors Interact with Different Viral Proteins

NASA Astrophysics Data System (ADS)

Sears, Amy E.; McGwire, Bradford S.; Roizman, Bernard

1991-06-01

Herpes simplex virus 1 attaches to at least two cell surface receptors. In polarized epithelial (Madin-Darby canine kidney; MDCK) cells one receptor is located in the apical surface and attachment to the cells requires the presence of glycoprotein C in the virus. The second receptor is located in the basal surface and does not require the presence of glycoprotein C. Exposure of MDCK cells at either the apical or basal surface to wild-type virus yields plaques and viral products whereas infection by a glycoprotein C-negative mutant yields identical results only after exposure of MDCK cells to virus at the basal surface. Multiple receptors for viral entry into cells expand the host range of the virus. The observation that glycoprotein C-negative mutants are infectious in many nonpolarized cell lines suggests that cells in culture may express more than one receptor and explains why genes that specify the viral proteins that recognize redundant receptors, like glycoprotein C, are expendable.

Mohs micrographic surgery for basal cell carcinomas: appropriateness of 'Rotterdam' criteria and predictive factors for three or more stages.

PubMed

Flohil, S C; van Dorst, A M J M; Nijsten, T; Martino Neumann, H A; Munte, K

2013-10-01

In the Netherlands basal cell carcinomas (BCC) are eligible for Mohs microscopic surgery (MMS) if certain criteria are fulfilled. To study the MMS indication criteria practised at the department of dermatology of the Erasmus University Medical Center, Rotterdam and to identify predictive factors for extensive subclinical tumour spread among BCCs eligible for MMS. Pre-operative patient and tumour characteristics were derived retrospectively between January 2nd 2006 and December 28th 2009 from 1174 patient records, accounting for 1464 BCCs. Multivariate logistic regression models were used to calculate crude and adjusted odds ratios (OR) with 95% confidence intervals (CI) for one vs. two or more stages and for narrow (≤ 2 stages) vs. extensive subclinical spread (≥ 3 stages). H-zone location [adjusted OR 1.51 (95% CI 1.16-1.96)], recurrent tumour [adjusted OR 1.50 (95% CI 1.11-2.02)], aggressive subtype [adjusted OR 1.25 (95% CI 1.01-1.56)] and tumour size ≥ 11 mm [adjusted OR 1.53 (95% CI 1.20-1.96)] were significantly associated with two or more stages. Predictive factors for extensive subclinical spread were recurrent tumour [adjusted OR 2.26 (95% CI 1.61-3.17)], tumour size ≥ 21 mm [adjusted OR 1.69 (95% CI 1.13-2.51)] and location in the H-zone [adjusted OR 1.68 (95% CI 1.15-2.46)]. 'Rotterdam' indication criteria used for MMS are appropriate. Predictors for extensive subclinical spread are important for patients' and surgeons' expectations prior to the operation about time span, defect size, reconstruction and possible associated morbidity. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

Microtubules Enable the Planar Cell Polarity of Airway Cilia

PubMed Central

Vladar, Eszter K.; Bayly, Roy D.; Sangoram, Ashvin; Scott, Matthew P.; Axelrod, Jeffrey D.

2012-01-01

Summary Background Airway cilia must be physically oriented along the longitudinal tissue axis for concerted, directional motility that is essential for proper mucociliary clearance. Results We show that Planar Cell Polarity (PCP) signaling specifies directionality and orients respiratory cilia. Within all airway epithelial cells a conserved set of PCP proteins shows interdependent, asymmetric junctional localization; non-autonomous signaling coordinates polarization between cells; and a polarized microtubule (MT) network is likely required for asymmetric PCP protein localization. We find that basal bodies dock after polarity of PCP proteins is established, are polarized nearly simultaneously, and refinement of basal body/cilium orientation continues during airway epithelial development. Unique to mature multiciliated cells, we identify PCP-regulated, planar polarized MTs that originate from basal bodies and interact, via their plus ends, with membrane domains associated with the PCP proteins Frizzled and Dishevelled. Disruption of MTs leads to misoriented cilia. Conclusions A conserved PCP pathway orients airway cilia by communicating polarity information from asymmetric membrane domains at the apical junctions, through MTs, to orient the MT and actin based network of ciliary basal bodies below the apical surface. PMID:23122850

Basal Cell Carcinoma Arising in a Breast Augmentation Scar.

PubMed

Edwards, Lisa R; Cresce, Nicole D; Russell, Mark A

2017-04-01

We report a case of a 46-year-old female who presented with a persistent lesion on the inferior right breast. The lesion was located within the scar from a breast augmentation procedure 12 years ago. The lesion had been treated as several conditions with no improvement. Biopsy revealed a superficial and nodular basal cell carcinoma, and the lesion was successfully removed with Mohs micrographic surgery. Basal cell carcinoma arising in a surgical scar is exceedingly rare with only 13 reported cases to date. This is the first reported case of basal cell carcinoma arising in a breast augmentation scar. We emphasize the importance of biopsy for suspicious lesions or those refractory to treatment, particularly those lesions that form within a scar. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Tumor suppression in basal keratinocytes via dual non-cell-autonomous functions of a Na,K-ATPase beta subunit

PubMed Central

Hatzold, Julia; Beleggia, Filippo; Herzig, Hannah; Altmüller, Janine; Nürnberg, Peter; Bloch, Wilhelm; Wollnik, Bernd; Hammerschmidt, Matthias

2016-01-01

The molecular pathways underlying tumor suppression are incompletely understood. Here, we identify cooperative non-cell-autonomous functions of a single gene that together provide a novel mechanism of tumor suppression in basal keratinocytes of zebrafish embryos. A loss-of-function mutation in atp1b1a, encoding the beta subunit of a Na,K-ATPase pump, causes edema and epidermal malignancy. Strikingly, basal cell carcinogenesis only occurs when Atp1b1a function is compromised in both the overlying periderm (resulting in compromised epithelial polarity and adhesiveness) and in kidney and heart (resulting in hypotonic stress). Blockade of the ensuing PI3K-AKT-mTORC1-NFκB-MMP9 pathway activation in basal cells, as well as systemic isotonicity, prevents malignant transformation. Our results identify hypotonic stress as a (previously unrecognized) contributor to tumor development and establish a novel paradigm of tumor suppression. DOI: http://dx.doi.org/10.7554/eLife.14277.001 PMID:27240166

980nm laser for difficult-to-treat basal cell carcinoma

NASA Astrophysics Data System (ADS)

Derjabo, A. D.; Cema, I.; Lihacova, I.; Derjabo, L.

2013-06-01

Begin basal cell carcinoma (BCC) is most common skin cancer over the world. There are around 20 modalities for BCC treatment. Laser surgery is uncommon option. We demonstrate our long term follow up results. Aim: To evaluate long term efficacy of a 980nm diode laser for the difficult-to-treat basal cell carcinoma. Materials and Methods: 167 patients with 173 basal cell carcinoma on the nose were treated with a 980 nm diode laser from May 1999 till May 2005 at Latvian Oncology center. All tumors were morphologically confirmed. 156 patients were followed for more than 5 years. Results: The lowest recurrence rate was observed in cases of superficial BCC, diameter<6mm bet the highest recurrence rate was in cases of infiltrative BCC and nodular recurrent BCC. Conclusions: 980 nm diode laser is useful tool in dermatology with high long term efficacy, good acceptance by the patients and good cosmetics results.

Cyclin D2 in the basal process of neural progenitors is linked to non-equivalent cell fates

PubMed Central

Tsunekawa, Yuji; Britto, Joanne M; Takahashi, Masanori; Polleux, Franck; Tan, Seong-Seng; Osumi, Noriko

2012-01-01

Asymmetric cell division plays an indispensable role during corticogenesis for producing new neurons while maintaining a self-renewing pool of apical progenitors. The cellular and molecular determinants favouring asymmetric division are not completely understood. Here, we identify a novel mechanism for generating cellular asymmetry through the active transportation and local translation of Cyclin D2 mRNA in the basal process. This process is regulated by a unique cis-regulatory sequence found in the 3′ untranslated region (3′UTR) of the mRNA. Unequal inheritance of Cyclin D2 protein to the basally positioned daughter cell with the basal process confers renewal of the apical progenitor after asymmetric division. Conversely, depletion of Cyclin D2 in the apically positioned daughter cell results in terminal neuronal differentiation. We demonstrate that Cyclin D2 is also expressed in the developing human cortex within similar domains, thus indicating that its role as a fate determinant is ancient and conserved. PMID:22395070

Endothelial Cell Hyperproliferation and Stratification in Uteroplacental Blood Vessels of the Black Mastiff Bat, Molossus rufus

PubMed Central

Rasweiler IV, J.J.; Badwaik, N.K.; Salame, G.; Abulafia, O.

2011-01-01

Placentation was studied histologically and immunocytochemically in black mastiff bats obtained at frequent intervals throughout pregnancy. These were bred in a captive colony or collected from a reproductively-synchronized wild population. During late pregnancy, the single fetus was largely sustained by a discoidal, hemochorial placenta located at the cranial end of the right uterine horn. This invariant positioning was determined by a vascular tuft that developed there both during early pregnancy and non-pregnant cycles. This provided a scaffold for early placental morphogenesis. As development proceeded, small arterioles and venules serving the tuft were converted to large uteroplacental vessels. Within the base of the placenta, these became lined by an unusual vascular epithelium composed of intermingled patches of multilayered endothelial cells and cytotrophoblast. Initially, the endothelium became multilayered by hypertrophy, proliferation, and infolding of its basal lamina. These created endothelial bilayers usually insinuated between basal laminae. The development of temporary gaps in the laminae then permitted further enlargement of the vessels and proliferation of the endothelial cells as monolayer sheets or chains. The latter were interconnected, forming a complex, stratified, cellular network associated with a prominent meshwork of basal laminae. Throughout much of pregnancy, these endothelial cells were cuboidal to columnar and possessed an abundance of basal glycoprotein granules presumably containing basal lamina precursors. The cells also expressed vimentin and frequently von Willebrand factor, but not cytokeratins or desmin. Pronounced thickening of the endothelia and amplification of their basal laminae likely evolved to greatly strengthen the walls of the uteroplacental vessels. PMID:21764447

Mammary Tumors Initiated by Constitutive Cdk2 Activation Contain an Invasive Basal-like Component1

PubMed Central

Corsino, Patrick E; Davis, Bradley J; Nörgaard, Peter H; Teoh Parker, Nicole N; Law, Mary; Dunn, William; Law, Brian K

2008-01-01

The basal-like subtype of breast cancer is associated with invasiveness, high rates of postsurgical recurrence, and poor prognosis. Aside from inactivation of the BRCA1 tumor-suppressor gene, little is known concerning the mechanisms that cause basal breast cancer or the mechanisms responsible for its invasiveness. Here, we show that the heterogeneous mouse mammary tumor virus-cyclin D1-Cdk2 (MMTV-D1K2) transgenic mouse mammary tumors contain regions of spindle-shaped cells expressing both luminal and myoepithelial markers. Cell lines cultured from these tumors exhibit the same luminal/myoepithelial mixed-lineage phenotype that is associated with human basal-like breast cancer and express a number of myoepithelial markers including cytokeratin 14, P-cadherin, α smooth muscle actin, and nestin. The MMTV-D1K2 tumor-derived cell lines form highly invasive tumors when injected into mouse mammary glands. Invasion is associated with E-cadherin localization to the cytoplasm or loss of E-cadherin expression. Cytoplasmic E-cadherin correlates with lack of colony formation in vitro and β-catenin and p120ctn localization to the cytoplasm. The data suggest that the invasiveness of these cell lines results from a combination of factors including mislocalization of E-cadherin, β-catenin, and p120ctn to the cytoplasm. Nestin expression and E-cadherin mislocalization were also observed in human basal-like breast cancer cell lines, suggesting that these results are relevant to human tumors. Together, these results suggest that abnormal Cdk2 activation may contribute to the formation of basal-like breast cancers. PMID:18953433

[Architectural ultrastructure of the human urinary transitional epithelium].

PubMed

Takayama, H; Konishi, T

1984-07-01

Human urinary bladder mucosa, confirmed to be normal by cystoscopic, histologic and bacteriologic examination, were obtained from four patients at prostatectomy and from two patients at an anti-VUR procedure. The luminal surface and the three dimensional architecture of the bladder mucosa were observed by scanning electron microscopy (SEM) after cryofracture of specimen and by transmission electron microscopy (TEM). The epithelium consists of superficial, intermediate and basal cells, and SEM and TEM showed that it was stratified. Intermediate cells reached the basal lamina by slender cytoplasmic processes but superficial cells were not directly in contact with the basal lamina. No pleomorphic or long microvilli were observed but short microvilli or granular protrusions were sparsely seen on the luminal surface of superficial cells. SEM of cryofractured surfaces revealed that cells from each cell layer were in contact with cellular junctions such as ridges, plicated projections and septum-like walls. Their junctions were more complicated with increasing depth of the cell layer. No pleomorphic or long microvilli were observed on any cell surface of the intermediate or basal cell layer. Under TEM, however, these junctional structures of ridges, plicated projections and septal walls appeared to be microvilli under TEM. Microvilli-like structures on TEM, therefore, have to be carefully distinguished from real microvilli. Careful observation is required when the presence of cells covered with microvilli is described as a sign of malignancy.

Cell polarity proteins and spermatogenesis.

PubMed

Gao, Ying; Xiao, Xiang; Lui, Wing-Yee; Lee, Will M; Mruk, Dolores; Cheng, C Yan

2016-11-01

When the cross-section of a seminiferous tubule from an adult rat testes is examined microscopically, Sertoli cells and germ cells in the seminiferous epithelium are notably polarized cells. For instance, Sertoli cell nuclei are found near the basement membrane. On the other hand, tight junction (TJ), basal ectoplasmic specialization (basal ES, a testis-specific actin-rich anchoring junction), gap junction (GJ) and desmosome that constitute the blood-testis barrier (BTB) are also located near the basement membrane. The BTB, in turn, divides the epithelium into the basal and the adluminal (apical) compartments. Within the epithelium, undifferentiated spermatogonia and preleptotene spermatocytes restrictively reside in the basal compartment whereas spermatocytes and post-meiotic spermatids reside in the adluminal compartment. Furthermore, the heads of elongating/elongated spermatids point toward the basement membrane with their elongating tails toward the tubule lumen. However, the involvement of polarity proteins in this unique cellular organization, in particular the underlying molecular mechanism(s) by which polarity proteins confer cellular polarity in the seminiferous epithelium is virtually unknown until recent years. Herein, we discuss latest findings regarding the role of different polarity protein complexes or modules and how these protein complexes are working in concert to modulate Sertoli cell and spermatid polarity. These findings also illustrate polarity proteins exert their effects through the actin-based cytoskeleton mediated by actin binding and regulatory proteins, which in turn modulate adhesion protein complexes at the cell-cell interface since TJ, basal ES and GJ utilize F-actin for attachment. We also propose a hypothetical model which illustrates the antagonistic effects of these polarity proteins. This in turn provides a unique mechanism to modulate junction remodeling in the testis to support germ cell transport across the epithelium in particular the BTB during the epithelial cycle of spermatogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Oncogenic Role of RhoGAPs in Basal-Like Breast Cancer

DTIC Science & Technology

2015-02-01

cell lines, and mouse models . c) In vivo tumorigenesis and metastasis assays. Milestones: Identify whether ArhGAP11A and RacGAP1 can promote tumor growth...also upregulated in basal (C3(I)-Tag) but not luminal (MMTV-Neu) genetically- engineered mouse models (Fig. 1B). At the protein level, RacGAP1 was...hypothesis that these RhoGAPs are indeed playing an oncogenic role in these cells. Human Tumors Mouse Model Tumors Normal Luminal A Basal-like Normal

Differential expression of extracellular matrix molecules and the alpha 6-integrins in the normal and neoplastic prostate.

PubMed Central

Knox, J. D.; Cress, A. E.; Clark, V.; Manriquez, L.; Affinito, K. S.; Dalkin, B. L.; Nagle, R. B.

1994-01-01

The epithelial basal lamina composition and integrin expression profile of normal and neoplastic human prostate was characterized using immunohistochemical analysis of frozen samples. The major components of the basal lamina surrounding normal acini were laminin, type IV collagen, entactin, and type VII collagen with variable amounts of tenascin. The basal lamina of neoplastic acini had a similar composition, except for the loss of type VII collagen, which was observed in all grades of carcinoma. The basal cells of the normal prostate express the alpha 6-, beta 1-, and beta 4-integrin subunits, suggesting that both the alpha 6 beta 1- and alpha 6 beta 4-integrin complexes are formed. In prostate carcinoma there is a complete loss of beta 4 expression and the alpha 6- and beta 1-integrin subunits, which are restricted to the basal and basal lateral surfaces of basal cells, are distributed diffusely throughout the cytoplasmic membrane. The differential expression of type VII collagen and beta 4 are discussed in relationship to their possible role in tumor progression. Images Figure 1 Figure 2 Figure 3 PMID:8030747

Prevention of Insulin-Induced Hypoglycemia in Type 1 Diabetes with Predictive Low Glucose Management System.

PubMed

Abraham, Mary B; de Bock, Martin; Paramalingam, Nirubasini; O'Grady, Michael J; Ly, Trang T; George, Carly; Roy, Anirban; Spital, Glenn; Karula, Sophy; Heels, Kristine; Gebert, Rebecca; Fairchild, Jan M; King, Bruce R; Ambler, Geoffrey R; Cameron, Fergus; Davis, Elizabeth A; Jones, Timothy W

2016-07-01

Sensor-augmented pump therapy (SAPT) with algorithms to predict impending low blood glucose and suspend insulin delivery has the potential to reduce hypoglycemia exposure. The aim of this study was to determine whether predictive low glucose management (PLGM) system is effective in preventing insulin-induced hypoglycemia in controlled experiments. Two protocols were used to induce hypoglycemia in an in-clinic environment. (A) Insulin bolus: Insulin was administered as a manual bolus through the pump. (B) Increased basal insulin: Hypoglycemia was induced by increasing basal rates overnight to 180%. For both protocols, participants were randomized and studied on 2 separate days; a control day with SAPT alone and an intervention day with SAPT and PLGM activated. The predictive algorithm was programmed to suspend basal insulin infusion when sensor glucose was predicted to be <80 mg/dL in 30 min. The primary outcome was the requirement for hypoglycemia treatment (symptomatic hypoglycemia or plasma glucose <50 mg/dL) and was compared in both control and intervention arms. With insulin bolus, 24/28 participants required hypoglycemia treatment with SAPT alone compared to 5/28 participants when PLGM was activated (P ≤ 0.001). With increased basal rates, all the eight SAPT-alone participants required treatment for hypoglycemia compared to only one with SAPT and PLGM. There was no post pump-suspend hyperglycemia with insulin bolus (P = 0.4) or increased basal rates (P = 0.69) in participants with 2-h pump suspension on intervention days. SAPT with PLGM reduced the requirement for hypoglycemia treatment following insulin-induced hypoglycemia in an in-clinic setting.

YAP and TAZ in epithelial stem cells: A sensor for cell polarity, mechanical forces and tissue damage.

PubMed

Elbediwy, Ahmed; Vincent-Mistiaen, Zoé I; Thompson, Barry J

2016-07-01

The YAP/TAZ family of transcriptional co-activators drives cell proliferation in epithelial tissues and cancers. Yet, how YAP and TAZ are physiologically regulated remains unclear. Here we review recent reports that YAP and TAZ act primarily as sensors of epithelial cell polarity, being inhibited when cells differentiate an apical membrane domain, and being activated when cells contact the extracellular matrix via their basal membrane domain. Apical signalling occurs via the canonical Crumbs/CRB-Hippo/MST-Warts/LATS kinase cascade to phosphorylate and inhibit YAP/TAZ. Basal signalling occurs via Integrins and Src family kinases to phosphorylate and activate YAP/TAZ. Thus, YAP/TAZ is localised to the nucleus in basal stem/progenitor cells and cytoplasm in differentiated squamous cells or columnar cells. In addition, other signals such as mechanical forces, tissue damage and possibly receptor tyrosine kinases (RTKs) can influence MST-LATS or Src family kinase activity to modulate YAP/TAZ activity. © 2016 The Authors BioEssays Published by WILEY Periodicals, Inc.

Three-dimensional spatial modeling of spines along dendritic networks in human cortical pyramidal neurons

PubMed Central

Larrañaga, Pedro; Benavides-Piccione, Ruth; Fernaud-Espinosa, Isabel; DeFelipe, Javier; Bielza, Concha

2017-01-01

We modeled spine distribution along the dendritic networks of pyramidal neurons in both basal and apical dendrites. To do this, we applied network spatial analysis because spines can only lie on the dendritic shaft. We expanded the existing 2D computational techniques for spatial analysis along networks to perform a 3D network spatial analysis. We analyzed five detailed reconstructions of adult human pyramidal neurons of the temporal cortex with a total of more than 32,000 spines. We confirmed that there is a spatial variation in spine density that is dependent on the distance to the cell body in all dendrites. Considering the dendritic arborizations of each pyramidal cell as a group of instances of the same observation (the neuron), we used replicated point patterns together with network spatial analysis for the first time to search for significant differences in the spine distribution of basal dendrites between different cells and between all the basal and apical dendrites. To do this, we used a recent variant of Ripley’s K function defined to work along networks. The results showed that there were no significant differences in spine distribution along basal arbors of the same neuron and along basal arbors of different pyramidal neurons. This suggests that dendritic spine distribution in basal dendritic arbors adheres to common rules. However, we did find significant differences in spine distribution along basal versus apical networks. Therefore, not only do apical and basal dendritic arborizations have distinct morphologies but they also obey different rules of spine distribution. Specifically, the results suggested that spines are more clustered along apical than in basal dendrites. Collectively, the results further highlighted that synaptic input information processing is different between these two dendritic domains. PMID:28662210

Three-dimensional spatial modeling of spines along dendritic networks in human cortical pyramidal neurons.

PubMed

Anton-Sanchez, Laura; Larrañaga, Pedro; Benavides-Piccione, Ruth; Fernaud-Espinosa, Isabel; DeFelipe, Javier; Bielza, Concha

2017-01-01

We modeled spine distribution along the dendritic networks of pyramidal neurons in both basal and apical dendrites. To do this, we applied network spatial analysis because spines can only lie on the dendritic shaft. We expanded the existing 2D computational techniques for spatial analysis along networks to perform a 3D network spatial analysis. We analyzed five detailed reconstructions of adult human pyramidal neurons of the temporal cortex with a total of more than 32,000 spines. We confirmed that there is a spatial variation in spine density that is dependent on the distance to the cell body in all dendrites. Considering the dendritic arborizations of each pyramidal cell as a group of instances of the same observation (the neuron), we used replicated point patterns together with network spatial analysis for the first time to search for significant differences in the spine distribution of basal dendrites between different cells and between all the basal and apical dendrites. To do this, we used a recent variant of Ripley's K function defined to work along networks. The results showed that there were no significant differences in spine distribution along basal arbors of the same neuron and along basal arbors of different pyramidal neurons. This suggests that dendritic spine distribution in basal dendritic arbors adheres to common rules. However, we did find significant differences in spine distribution along basal versus apical networks. Therefore, not only do apical and basal dendritic arborizations have distinct morphologies but they also obey different rules of spine distribution. Specifically, the results suggested that spines are more clustered along apical than in basal dendrites. Collectively, the results further highlighted that synaptic input information processing is different between these two dendritic domains.

Fluorescence confocal mosaicing microscopy of basal cell carcinomas ex vivo: demonstration of rapid surgical pathology with high sensitivity and specificity

NASA Astrophysics Data System (ADS)

Gareau, Daniel S.; Karen, Julie K.; Dusza, Stephen W.; Tudisco, Marie; Nehal, Kishwer S.; Rajadhyaksha, Milind

2009-02-01

Mohs surgery, for the precise removal of basal cell carcinomas (BCCs), consists of a series of excisions guided by the surgeon's examination of the frozen histology of the previous excision. The histology reveals atypical nuclear morphology, identifying cancer. The preparation of frozen histology is accurate but labor-intensive and slow. Nuclear pathology can be achieved by staining with acridine orange (1 mM, 20 s) BCCs in Mohs surgical skin excisions within 5-9 minutes, compared to 20-45 for frozen histology. For clinical utility, images must have high contrast and high resolution. We report tumor contrast of 10-100 fold over the background dermis and submicron (diffraction limited) resolution over a cm field of view. BCCs were detected with an overall sensitivity of 96.6%, specificity of 89.2%, positive predictive value of 93.0% and negative predictive value of 94.7%. The technique was therefore accurate for normal tissue as well as tumor. We conclude that fluorescence confocal mosaicing serves as a sensitive and rapid pathological tool. Beyond Mohs surgery, this technology may be extended to suit other pathological needs with the development of new contrast agents. The technique reported here accurately detects all subtypes of BCC in skin excisions, including the large nodular, small micronodular, and tiny sclerodermaform tumors. However, this technique may be applicable to imaging tissue that is larger, more irregular and of various mechanical compliances with further engineering of the tissue mounting and staging mechanisms.

Sonidegib for the treatment of advanced basal cell carcinoma: a comprehensive review of sonidegib and the BOLT trial with 12-month update.

PubMed

Chen, Leon; Silapunt, Sirunya; Migden, Michael R

2016-09-01

The Hedgehog inhibitors are promising alternative for patients with advanced basal cell carcinoma that are not amenable to radiotherapy or surgery. Sonidegib, also known as LDE225, is an orally available SMO antagonist that was recently approved by the US FDA for the treatment of patients with locally advanced basal cell carcinoma. This article will provide an overview of the pharmacology and pharmacokinetics of sonidegib and in-depth analysis of the BOLT trial with additional data from the 12-month update. The present challenges associated with Hedgehog inhibitors will also be discussed.

Ex vivo-expanded bone marrow CD34(+) for acute myocardial infarction treatment: in vitro and in vivo studies.

PubMed

Gunetti, Monica; Noghero, Alessio; Molla, Fabiola; Staszewsky, Lidia Irene; de Angelis, Noeleen; Soldo, Annarita; Russo, Ilaria; Errichiello, Edoardo; Frasson, Chiara; Rustichelli, Deborah; Ferrero, Ivana; Gualandris, Anna; Berger, Massimo; Geuna, Massimo; Scacciatella, Paolo; Basso, Giuseppe; Marra, Sebastiano; Bussolino, Federico; Latini, Roberto; Fagioli, Franca

2011-10-01

Bone marrow (BM)-derived cells appear to be a promising therapeutic source for the treatment of acute myocardial infarction (AMI). However, the quantity and quality of the cells to be used, along with the appropriate time of administration, still need to be defined. We thus investigated the use of BM CD34(+)-derived cells as cells suitable for a cell therapy protocol (CTP) in the treatment of experimental AMI. The need for a large number of cells was satisfied by the use of a previously established protocol allowing the expansion of human CD34(+) cells isolated from neonatal and adult hematopoietic tissues. We evaluated gene expression, endothelial differentiation potential and cytokine release by BM-derived cells during in vitro culture. Basal and expanded CD34(+) cells were used as a delivery product in a murine AMI model consisting of a coronary artery ligation (CAL). Cardiac function recovery was evaluated after injecting basal or expanded cells. Gene expression analysis of in vitro-expanded cells revealed that endothelial markers were up-regulated during culture. Moreover, expanded cells generated a CD14(+) subpopulation able to differentiate efficiently into VE-cadherin-expressing cells. In vivo, we observed a cardiac function recovery in mice sequentially treated with basal and expanded cells injected 4 h and 7 days after CAL, respectively. Our data suggest that combining basal and expanded BM-derived CD34(+) cells in a specific temporal pattern of administration might represent a promising strategy for a successful cell-based therapy.

A Rare Case of Giant Basal Cell Carcinoma of the Abdominal Wall: Excision and Immediate Reconstruction with a Pedicled Deep Inferior Epigastric Artery Perforator (DIEP) Flap.

PubMed

Di Lorenzo, Sara; Zabbia, Giovanni; Corradino, Bartolo; Tripoli, Massimiliano; Pirrello, Roberto; Cordova, Adriana

2017-12-04

BACKGROUND Basal cell carcinoma (BCC) greater than 5 cm in diameter is called giant basal cell carcinoma (GBCC), or super giant basal cell carcinoma if it has a diameter larger than 20 cm. Giant BCC only accounts for 0.5% of BCCs and super giant BCC is exceedingly rare. On account of their rarity, there are no established guidelines for GBCC treatment. CASE REPORT We describe a peculiar case of an 82-year-old woman with a GBCC carcinoma of the lower abdominal wall. The tumor was surgically removed with ipsilateral inguinal lymph nodes and the abdominal wall was reconstructed immediately with a pedicled deep inferior epigastric artery perforator (DIEP) flap. CONCLUSIONS Treatment of giant basal cell carcinoma is often difficult, especially in elderly patients with poor general health and multiple pathologies. The pedicled DIEP flap is rotated to cover the loss of substance without tension, and it is easy to harvest and transfer. This flap allowed a good result without local or systemic complication. We present this report as a reminder of the occasional occurrence of extremely aggressive BCCs. We believe that, especially for rare tumors like these, it is very useful for the entire scientific community to publish these cases and the therapeutic strategies used to treat them.

Modification of the activity of cell wall-bound peroxidase by hypergravity in relation to the stimulation of lignin formation in azuki bean epicotyls

NASA Astrophysics Data System (ADS)

Wakabayashi, Kazuyuki; Nakano, Saho; Soga, Kouichi; Hoson, Takayuki

Lignin is a component of cell walls of terrestrial plants, which provides cell walls with the mechanical rigidity. Lignin is a phenolic polymer with high molecular mass and formed by the polymerization of phenolic substances on a cellulosic matrix. The polymerization is catalyzed by cell wall-bound peroxidase, and thus the activity of this enzyme regulates the rate of formation of lignin. In the present study, the changes in the lignin content and the activity of cell wall peroxidase were investigated along epicotyls of azuki bean seedlings grown under hypergravity conditions. The endogenous growth occurred primarily in the upper regions of the epicotyl and no growth was detected in the middle or basal regions. The amounts of acetyl bromide-soluble lignin increased from the upper to the basal regions of epicotyls. The lignin content per unit length in the basal region was three times higher than that in the upper region. Hypergravity treatment at 300 g for 6 h stimulated the increase in the lignin content in all regions of epicotyls, particularly in the basal regions. The peroxidase activity in the protein fraction extracted from the cell wall preparation with a high ionic strength buffer also increased gradually toward the basal region, and hypergravity treatment clearly increased the activity in all regions. There was a close correlation between the lignin content and the enzyme activity. These results suggest that gravity stimuli modulate the activity of cell wall-bound peroxidase, which, in turn, causes the stimulation of the lignin formation in stem organs.

Defining High-Risk Precursor Signaling to Advance Breast Cancer Risk Assessment and Prevention

DTIC Science & Technology

2017-03-01

KEYWORDS: 3. ACCOMPLISHMENTS: Aim 1: Functional analysis of progenitor and stem cells in high-risk tissues. Major Task 1Functional...and stem cells in high-risk tissues. Major Task 1: Quantitation of LP (Luminal Progenitor) and basal stem cell (MASC) populations A. Quantitation of...LP and basal stem cell (MASC) populations We have continued to add patients to the cohorts between months 12 and 24. (This reporting period

Tumor suppressor berberine binds VASP to inhibit cell migration in basal-like breast cancer.

PubMed

Su, Ke; Hu, Pengchao; Wang, Xiaolan; Kuang, Changchun; Xiang, Qingmin; Yang, Fang; Xiang, Jin; Zhu, Shan; Wei, Lei; Zhang, Jingwei

2016-07-19

Berberine is a plant-derived compound used in traditional Chinese medicine, which has been shown to inhibit cell proliferation and migration in breast cancer. On the other hand, vasodilator-stimulated phosphoprotein (VASP) promotes actin filament elongation and cell migration. We previously showed that VASP is overexpressed in high-motility breast cancer cells. Here we investigated whether the anti-tumorigenic effects of berberine are mediated by binding VASP in basal-like breast cancer. Our results show that berberine suppresses proliferation and migration of MDA-MB-231 cells as well as tumor growth in MDA-MB-231 nude mouse xenografts. We also show that berberine binds to VASP, inducing changes in its secondary structure and inhibits actin polymerization. Our study reveals the mechanism underlying berberine's inhibition of cell proliferation and migration in basal-like breast cancer, highlighting the use of berberine as a potential adjuvant therapeutic agent.

Tumor suppressor berberine binds VASP to inhibit cell migration in basal-like breast cancer

PubMed Central

Wang, Xiaolan; Kuang, Changchun; Xiang, Qingmin; Yang, Fang; Xiang, Jin; Zhu, Shan; Wei, Lei; Zhang, Jingwei

2016-01-01

Berberine is a plant-derived compound used in traditional Chinese medicine, which has been shown to inhibit cell proliferation and migration in breast cancer. On the other hand, vasodilator-stimulated phosphoprotein (VASP) promotes actin filament elongation and cell migration. We previously showed that VASP is overexpressed in high-motility breast cancer cells. Here we investigated whether the anti-tumorigenic effects of berberine are mediated by binding VASP in basal-like breast cancer. Our results show that berberine suppresses proliferation and migration of MDA-MB-231 cells as well as tumor growth in MDA-MB-231 nude mouse xenografts. We also show that berberine binds to VASP, inducing changes in its secondary structure and inhibits actin polymerization. Our study reveals the mechanism underlying berberine's inhibition of cell proliferation and migration in basal-like breast cancer, highlighting the use of berberine as a potential adjuvant therapeutic agent. PMID:27322681

Basal body assembly in ciliates: the power of numbers

PubMed Central

Pearson, Chad G.; Winey, Mark

2009-01-01

Centrioles perform the dual functions of organizing both centrosomes and cilia. The biogenesis of nascent centrioles is an essential cellular event that is tightly coupled to the cell cycle so that each cell contains only two or four centrioles at any given point in the cell cycle. The assembly of centrioles and their analogs, basal bodies, is well characterized at the ultrastructural level whereby structural modules are built into a functional organelle. Genetic studies in model organisms combined with proteomic, bioinformatic, and identifying ciliary disease gene orthologs have revealed a wealth of molecules requiring further analysis to determine their roles in centriole duplication, assembly, and function. Nonetheless, at this stage our understanding of how molecular components interact to build new centrioles and basal bodies is limited. The ciliates, Tetrahymena and Paramecium, historically have been the subject of cytological and genetic study of basal bodies. Recent advances in the ciliate genetic and molecular toolkit have placed these model organisms in a favorable position to study the molecular mechanisms of centriole and basal body assembly. PMID:19192246

SOX2 and PI3K Cooperate to Induce and Stabilize a Squamous-Committed Stem Cell Injury State during Lung Squamous Cell Carcinoma Pathogenesis

PubMed Central

Kim, Bo Ram; Van de Laar, Emily; Tarumi, Shintaro; Hasenoeder, Stefan; Wang, Dennis; Virtanen, Carl; Bandarchi, Bizhan; Pham, Nhu An; Lee, Sharon; Keshavjee, Shaf; Tsao, Ming-Sound; Moghal, Nadeem

2016-01-01

Although cancers are considered stem cell diseases, mechanisms involving stem cell alterations are poorly understood. Squamous cell carcinoma (SQCC) is the second most common lung cancer, and its pathogenesis appears to hinge on changes in the stem cell behavior of basal cells in the bronchial airways. Basal cells are normally quiescent and differentiate into mucociliary epithelia. Smoking triggers a hyperproliferative response resulting in progressive premalignant epithelial changes ranging from squamous metaplasia to dysplasia. These changes can regress naturally, even with chronic smoking. However, for unknown reasons, dysplasias have higher progression rates than earlier stages. We used primary human tracheobronchial basal cells to investigate how copy number gains in SOX2 and PIK3CA at 3q26-28, which co-occur in dysplasia and are observed in 94% of SQCCs, may promote progression. We find that SOX2 cooperates with PI3K signaling, which is activated by smoking, to initiate the squamous injury response in basal cells. This response involves SOX9 repression, and, accordingly, SOX2 and PI3K signaling levels are high during dysplasia, while SOX9 is not expressed. By contrast, during regeneration of mucociliary epithelia, PI3K signaling is low and basal cells transiently enter a SOX2LoSOX9Hi state, with SOX9 promoting proliferation and preventing squamous differentiation. Transient reduction in SOX2 is necessary for ciliogenesis, although SOX2 expression later rises and drives mucinous differentiation, as SOX9 levels decline. Frequent coamplification of SOX2 and PIK3CA in dysplasia may, thus, promote progression by locking basal cells in a SOX2HiSOX9Lo state with active PI3K signaling, which sustains the squamous injury response while precluding normal mucociliary differentiation. Surprisingly, we find that, although later in invasive carcinoma SOX9 is generally expressed at low levels, its expression is higher in a subset of SQCCs with less squamous identity and worse clinical outcome. We propose that early pathogenesis of most SQCCs involves stabilization of the squamous injury state in stem cells through copy number gains at 3q, with the pro-proliferative activity of SOX9 possibly being exploited in a subset of SQCCs in later stages. PMID:27880766

Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool.

PubMed

Mesa, Kailin R; Rompolas, Panteleimon; Zito, Giovanni; Myung, Peggy; Sun, Thomas Y; Brown, Samara; Gonzalez, David G; Blagoev, Krastan B; Haberman, Ann M; Greco, Valentina

2015-06-04

Tissue homeostasis is achieved through a balance of cell production (growth) and elimination (regression). In contrast to tissue growth, the cells and molecular signals required for tissue regression remain unknown. To investigate physiological tissue regression, we use the mouse hair follicle, which cycles stereotypically between phases of growth and regression while maintaining a pool of stem cells to perpetuate tissue regeneration. Here we show by intravital microscopy in live mice that the regression phase eliminates the majority of the epithelial cells by two distinct mechanisms: terminal differentiation of suprabasal cells and a spatial gradient of apoptosis of basal cells. Furthermore, we demonstrate that basal epithelial cells collectively act as phagocytes to clear dying epithelial neighbours. Through cellular and genetic ablation we show that epithelial cell death is extrinsically induced through transforming growth factor (TGF)-β activation and mesenchymal crosstalk. Strikingly, our data show that regression acts to reduce the stem cell pool, as inhibition of regression results in excess basal epithelial cells with regenerative abilities. This study identifies the cellular behaviours and molecular mechanisms of regression that counterbalance growth to maintain tissue homeostasis.

Basal-body-associated macromolecules: a continuing debate.

PubMed

Pierre Mignot, J; Brugerolle, G; Didier, P; Bornens, M

1993-07-01

Controversy over the possibility that centrioles/basal bodies contain nucleic acids has overshadowed results demonstrating other macromolecules in the lumen of these organelles. Glycogen particles, which are known to be present within the lumen of the centriole/basal body of sperm cells, have now been found in basal bodies of protists belonging to three different groups. Here, we extend the debate on a role for RNA in basal body/centriole function and speculate on the origin and the function of centriolar glycogen.

Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance

PubMed Central

West, John D; Dorà, Natalie J; Collinson, J Martin

2015-01-01

In this review we evaluate evidence for three different hypotheses that explain how the corneal epithelium is maintained. The limbal epithelial stem cell (LESC) hypothesis is most widely accepted. This proposes that stem cells in the basal layer of the limbal epithelium, at the periphery of the cornea, maintain themselves and also produce transient (or transit) amplifying cells (TACs). TACs then move centripetally to the centre of the cornea in the basal layer of the corneal epithelium and also replenish cells in the overlying suprabasal layers. The LESCs maintain the corneal epithelium during normal homeostasis and become more active to repair significant wounds. Second, the corneal epithelial stem cell (CESC) hypothesis postulates that, during normal homeostasis, stem cells distributed throughout the basal corneal epithelium, maintain the tissue. According to this hypothesis, LESCs are present in the limbus but are only active during wound healing. We also consider a third possibility, that the corneal epithelium is maintained during normal homeostasis by proliferation of basal corneal epithelial cells without any input from stem cells. After reviewing the published evidence, we conclude that the LESC and CESC hypotheses are consistent with more of the evidence than the third hypothesis, so we do not consider this further. The LESC and CESC hypotheses each have difficulty accounting for one main type of evidence so we evaluate the two key lines of evidence that discriminate between them. Finally, we discuss how lineage-tracing experiments have begun to resolve the debate in favour of the LESC hypothesis. Nevertheless, it also seems likely that some basal corneal epithelial cells can act as long-term progenitors if limbal stem cell function is compromised. Thus, this aspect of the CESC hypothesis may have a lasting impact on our understanding of corneal epithelial maintenance, even if it is eventually shown that stem cells are restricted to the limbus as proposed by the LESC hypothesis. PMID:25815115

Cationic Phosphorus Dendrimer Enhances Photodynamic Activity of Rose Bengal against Basal Cell Carcinoma Cell Lines.

PubMed

Dabrzalska, Monika; Janaszewska, Anna; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

2017-05-01

In the last couple of decades, photodynamic therapy emerged as a useful tool in the treatment of basal cell carcinoma. However, it still meets limitations due to unfavorable properties of photosensitizers such as poor solubility or lack of selectivity. Dendrimers, polymers widely studied in biomedical field, may play a role as photosensitizer carriers and improve the efficacy of photodynamic treatment. Here, we describe the evaluation of an electrostatic complex of cationic phosphorus dendrimer and rose bengal in such aspects as singlet oxygen production, cellular uptake, and phototoxicity against three basal cell carcinoma cell lines. Rose bengal-cationic dendrimer complex in molar ratio 5:1 was compared to free rose bengal. Obtained results showed that the singlet oxygen production in aqueous medium was significantly higher for the complex than for free rose bengal. The cellular uptake of the complex was 2-7-fold higher compared to a free photosensitizer. Importantly, rose bengal, rose bengal-dendrimer complex, and dendrimer itself showed no dark toxicity against all three cell lines. Moreover, we observed that phototoxicity of the complex was remarkably enhanced presumably due to high cellular uptake. On the basis of the obtained results, we conclude that rose bengal-cationic dendrimer complex has a potential in photodynamic treatment of basal cell carcinoma.

Endocochlear potential generation is associated with intercellular communication in the stria vascularis: structural analysis in the viable dominant spotting mouse mutant.

PubMed

Carlisle, L; Steel, K; Forge, A

1990-11-01

Deafness in the viable dominant spotting mouse mutant is due to a primary defect of the stria vascularis which results in absence of the positive endocochlear potential in scala media. Endocochlear potentials were measured and the structure of stria vascularis of mutants with potentials close to zero was compared with that in normal littermate controls by use of morphometric methods. The stria vascularis was significantly thinner in mutants. Marginal cells were not significantly different from controls in terms of volume density or intramembrane particle density but the network density of tight junctions was significantly reduced in the mutants. A virtual absence of gap junctions between basal cells and marginal or intermediate cells was observed, but intramembrane particle density and junctional complexes between adjacent basal cells were not different from controls. The volume density of basal cells was significantly greater in mutants. Intermediate cells accounted for a significantly smaller volume density of the stria vascularis in mutants and had a lower density of intramembrane particles than controls. Melanocytes were not identified in the stria vascularis of mutants. These results suggest that communication between marginal, intermediate and basal cells might be important to the normal function of the stria vascularis.

Loss of Centrobin Enables Daughter Centrioles to Form Sensory Cilia in Drosophila.

PubMed

Gottardo, Marco; Pollarolo, Giulia; Llamazares, Salud; Reina, Jose; Riparbelli, Maria G; Callaini, Giuliano; Gonzalez, Cayetano

2015-08-31

Sensory cilia are organelles that convey information to the cell from the extracellular environment. In vertebrates, ciliary dysfunction results in ciliopathies that in humans comprise a wide spectrum of developmental disorders. In Drosophila, sensory cilia are found only in the neurons of type I sensory organs, but ciliary dysfunction also has dramatic consequences in this organism because it impairs the mechanosensory properties of bristles and chaetae and leads to uncoordination, a crippling condition that causes lethality shortly after eclosion. The cilium is defined by the ciliary membrane, a protrusion of the cell membrane that envelops the core structure known as the axoneme, a microtubule array that extends along the cilium from the basal body. In vertebrates, basal body function requires centriolar distal and subdistal appendages and satellites. Because these structures are acquired through centriole maturation, only mother centrioles can serve as basal bodies. Here, we show that although centriole maturity traits are lacking in Drosophila, basal body fate is reserved to mother centrioles in Drosophila type I neurons. Moreover, we show that depletion of the daughter-centriole-specific protein Centrobin (CNB) enables daughter centrioles to dock on the cell membrane and to template an ectopic axoneme that, although structurally defective, protrudes out of the cell and is enveloped by a ciliary membrane. Conversely, basal body capability is inhibited in mother centrioles modified to carry CNB. These results reveal the crucial role of CNB in regulating basal body function in Drosophila ciliated sensory organs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Centrioles want to move out and make cilia.

PubMed

Pearson, Chad G; Culver, Brady P; Winey, Mark

2007-09-01

Cilia formation in mammalian cells requires basal bodies that are either derived from centrioles that transition from their cytoplasmic role in centrosome organization or that form en masse in multiciliated cells. Several recent studies have begun to uncover the links between centriole duplication and their transformation to basal bodies.

Basal cell carcinoma of the nipple. Report of two cases.

PubMed

Cain, R J; Sau, P; Benson, P M

1990-02-01

Two cases of basal cell carcinoma of the nipple are presented, bringing the total number of reported cases to 15. The majority, including our two patients, are elderly men. This finding suggests a causal role of exposure to ultraviolet radiation. In our cases excision was curative.

Identification of symplasmic domains in the embryo and seed of Sedum acre L. (Crassulaceae).

PubMed

Wróbel-Marek, Justyna; Kurczyńska, Ewa; Płachno, Bartosz J; Kozieradzka-Kiszkurno, Małgorzata

2017-03-01

Our study demonstrated that symplasmic communication between Sedum acre seed compartments and the embryo proper is not uniform. The presence of plasmodesmata (PD) constitutes the structural basis for information exchange between cells, and symplasmic communication is involved in the regulation of cell differentiation and plant development. Most recent studies concerning an analysis of symplasmic communication between seed compartments and the embryo have been predominantly performed on Arabidopsis thaliana. The results presented in this paper describe the analysis of symplasmic communication on the example of Sedum acre seeds, because the ultrastructure of the seed compartments and the embryo proper, including the PD, have already been described, and this species represents an embryonic type of development different to Arabidopsis. Moreover, in this species, an unusual electron-dense dome associated with plasmodesmata on the border between the basal cell/chalazal suspensor cells and the basal cell/the endosperm has been described. This prompted the question as to whether these plasmodesmata are functional. Thus, the aim of this study was to describe the movement of symplasmic transport fluorochromes between different Sedum seed compartments, with particular emphasis on the movement between the basal cell and the embryo proper and endosperm, to answer the following questions: (1) are seeds divided into symplasmic domains; (2) if so, are they stable or do they change with the development? The results have shown that symplasmic tracers movement: (a) from the external integument to internal integument is restricted; (b) from the basal cell to the other part of the embryo proper and from the basal cell to the endosperm is also restricted; (c) the embryo is a single symplasmic domain with respect to molecules of a molecular weight below 0.5 kDa.

Origin of Ameloblastoma From Basal Cells of the Oral Epithelium- Establishing the Relation Using Neuroectodermal Markers

PubMed Central

Suneela, S; Narayan, T V; Shreedhar, Balasundari; Mohanty, Leeky; Shenoy, Sadhana; Swaminathan, Uma

2014-01-01

Background and Objectives: Basal cell layer of the oral epithelium has been rightfully regarded as a potential source of odontogenic tumours and cysts, but, without substantial evidence. Also, whether the basal cell layer retains within it, some properties of ectomesenchyme, which was imbibed during the early embryogenesis and hence its neuroectodermal relation, is not known. Here, an attempt is made to establish the hidden neuroectodermal potential of the oral epithelium, especially the basal layer, by observing the expression of known neuroectodermal markers, NSE (Neuron Specific Enolase), Synaptophysin and CD99. The expression of the same markers has also been studied in Ameloblastoma, connecting it with oral epithelium, in turn establishing basal cell layer as a potential source of Ameloblastoma. Materials and Methods: Sections of formalin fixed, paraffin embedded tissue samples of 20 cases of Ameloblastoma and 10 cases of Normal Retromolar mucosa, were stained immunohistochemically with NSE, Synaptophysin, CD99 and also with CK-19 and evaluated for positive expression. Results: Positive reaction was obtained in all the cases of Ameloblastoma and NRM (Normal Retromolar mucosa) with NSE, all the cases of Ameloblastoma and eight cases of NRM with Synaptophysin and in six cases of Ameloblastoma and NRM with CD99. The staining was diffuse and more marked in case of NSE than Synaptophysin and CD99. CK19 staining done to assure that the tissue antigenicity was maintained was positive in all the samples. Interpretation and Conclusion: A strong relationship between the neuroectoderm, Ameloblastoma and the basal layer of the oral epithelium is established by the study. It favours the hypothesis that the basal cell layer of oral mucosa may be the sought out culprit in most cases of the Ameloblastomas, especially those occurring in the non-tooth bearing area. This would call for the need to incorporate additional therapy in the form of mucosal striping along with the conventional treatment. PMID:25478446

Sensitizing basal-like breast cancer to chemotherapy using nanoparticles conjugated with interference peptide

NASA Astrophysics Data System (ADS)

Sorolla, A.; Ho, D.; Wang, E.; Evans, C. W.; Ormonde, C. F. G.; Rashwan, R.; Singh, R.; Iyer, K. Swaminathan; Blancafort, P.

2016-04-01

Basal-like breast cancers are highly aggressive malignancies associated with very poor prognosis. Although these cancers may initially respond to first-line treatment, they become highly resistant to standard chemotherapy in the metastatic setting. Chemotherapy resistance in basal-like breast cancers is associated with highly selective overexpression of the homeobox transcription factor Engrailed 1 (EN1). Herein, we propose a novel therapeutic strategy using poly(glycidyl methacrylate) nanoparticles decorated with poly(acrylic acid) that enable dual delivery of docetaxel and interference peptides designed to block or inhibit EN1 (EN1-iPep). We demonstrate that EN1-iPep is highly selective in inducing apoptotic cell death in basal-like cancer cells with negligible effects in a non-neoplastic human mammary epithelial cell line. Furthermore, we show that treatment with EN1-iPep results in a highly synergistic pharmacological interaction with docetaxel in inhibiting cancer cell growth. The incorporation of these two agents in a single nanoformulation results in greater anticancer efficacy than current nanoparticle-based treatments used in the clinical setting.Basal-like breast cancers are highly aggressive malignancies associated with very poor prognosis. Although these cancers may initially respond to first-line treatment, they become highly resistant to standard chemotherapy in the metastatic setting. Chemotherapy resistance in basal-like breast cancers is associated with highly selective overexpression of the homeobox transcription factor Engrailed 1 (EN1). Herein, we propose a novel therapeutic strategy using poly(glycidyl methacrylate) nanoparticles decorated with poly(acrylic acid) that enable dual delivery of docetaxel and interference peptides designed to block or inhibit EN1 (EN1-iPep). We demonstrate that EN1-iPep is highly selective in inducing apoptotic cell death in basal-like cancer cells with negligible effects in a non-neoplastic human mammary epithelial cell line. Furthermore, we show that treatment with EN1-iPep results in a highly synergistic pharmacological interaction with docetaxel in inhibiting cancer cell growth. The incorporation of these two agents in a single nanoformulation results in greater anticancer efficacy than current nanoparticle-based treatments used in the clinical setting. Electronic supplementary information (ESI) available. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6ob00583g

SLC20A2 DEFICIENCY IN MICE LEADS TO ELEVATED PHOSPHATE LEVELS IN CEREBROSPINAL FLUID AND GLYMPHATIC PATHWAY-ASSOCIATED ARTERIOLAR CALCIFICATION, AND RECAPITULATES HUMAN IDIOPATHIC BASAL GANGLIA CALCIFICATION

PubMed Central

Wallingford, MC; Chia, J; Leaf, EM; Borgeia, S; Chavkin, NW; Sawangmake, C; Marro, K; Cox, TC; Speer, MY; Giachelli, CM

2016-01-01

Idiopathic basal ganglia calcification is a brain calcification disorder that has been genetically linked to autosomal dominant mutations in the sodium-dependent phosphate co-transporter, SLC20A2. The mechanisms whereby deficiency of Slc20a2 leads to basal ganglion calcification are unknown. In the mouse brain, we found that Slc20a2 was expressed in tissues that produce and/or regulate cerebrospinal fluid, including choroid plexus, ependyma and arteriolar smooth muscle cells. Haploinsufficient Slc20a2 +/− mice developed age-dependent basal ganglia calcification that formed in glymphatic pathway-associated arterioles. Slc20a2 deficiency uncovered phosphate homeostasis dysregulation characterized by abnormally high cerebrospinal fluid phosphate levels and hydrocephalus, in addition to basal ganglia calcification. Slc20a2 siRNA knockdown in smooth muscle cells revealed increased susceptibility to high phosphate-induced calcification. These data suggested that loss of Slc20a2 led to dysregulated phosphate homeostasis and enhanced susceptibility of arteriolar smooth muscle cells to elevated phosphate-induced calcification. Together, dysregulated cerebrospinal fluid phosphate and enhanced smooth muscle cell susceptibility may predispose to glymphatic pathway-associated arteriolar calcification. PMID:26822507

Endothelial induced EMT in breast epithelial cells with stem cell properties.

PubMed

Sigurdsson, Valgardur; Hilmarsdottir, Bylgja; Sigmundsdottir, Hekla; Fridriksdottir, Agla J R; Ringnér, Markus; Villadsen, Rene; Borg, Ake; Agnarsson, Bjarni A; Petersen, Ole William; Magnusson, Magnus K; Gudjonsson, Thorarinn

2011-01-01

Epithelial to mesenchymal transition (EMT) is a critical event in cancer progression and is closely linked to the breast epithelial cancer stem cell phenotype. Given the close interaction between the vascular endothelium and cancer cells, especially at the invasive front, we asked whether endothelial cells might play a role in EMT. Using a 3D culture model we demonstrate that endothelial cells are potent inducers of EMT in D492 an immortalized breast epithelial cell line with stem cell properties. Endothelial induced mesenchymal-like cells (D492M) derived from D492, show reduced expression of keratins, a switch from E-Cadherin (E-Cad) to N-Cadherin (N-Cad) and enhanced migration. Acquisition of cancer stem cell associated characteristics like increased CD44(high)/CD24(low) ratio, resistance to apoptosis and anchorage independent growth was also seen in D492M cells. Endothelial induced EMT in D492 was partially blocked by inhibition of HGF signaling. Basal-like breast cancer, a vascular rich cancer with stem cell properties and adverse prognosis has been linked with EMT. We immunostained several basal-like breast cancer samples for endothelial and EMT markers. Cancer cells close to the vascular rich areas show no or decreased expression of E-Cad and increased N-Cad expression suggesting EMT. Collectively, we have shown in a 3D culture model that endothelial cells are potent inducers of EMT in breast epithelial cells with stem cell properties. Furthermore, we demonstrate that basal-like breast cancer contains cells with an EMT phenotype, most prominently close to vascular rich areas of these tumors. We conclude that endothelial cells are potent inducers of EMT and may play a role in progression of basal-like breast cancer.

Endothelial Induced EMT in Breast Epithelial Cells with Stem Cell Properties

PubMed Central

Sigurdsson, Valgardur; Hilmarsdottir, Bylgja; Sigmundsdottir, Hekla; Fridriksdottir, Agla J. R.; Ringnér, Markus; Villadsen, Rene; Borg, Ake; Agnarsson, Bjarni A.; Petersen, Ole William; Magnusson, Magnus K.; Gudjonsson, Thorarinn

2011-01-01

Epithelial to mesenchymal transition (EMT) is a critical event in cancer progression and is closely linked to the breast epithelial cancer stem cell phenotype. Given the close interaction between the vascular endothelium and cancer cells, especially at the invasive front, we asked whether endothelial cells might play a role in EMT. Using a 3D culture model we demonstrate that endothelial cells are potent inducers of EMT in D492 an immortalized breast epithelial cell line with stem cell properties. Endothelial induced mesenchymal-like cells (D492M) derived from D492, show reduced expression of keratins, a switch from E-Cadherin (E-Cad) to N-Cadherin (N-Cad) and enhanced migration. Acquisition of cancer stem cell associated characteristics like increased CD44high/CD24low ratio, resistance to apoptosis and anchorage independent growth was also seen in D492M cells. Endothelial induced EMT in D492 was partially blocked by inhibition of HGF signaling. Basal-like breast cancer, a vascular rich cancer with stem cell properties and adverse prognosis has been linked with EMT. We immunostained several basal-like breast cancer samples for endothelial and EMT markers. Cancer cells close to the vascular rich areas show no or decreased expression of E-Cad and increased N-Cad expression suggesting EMT. Collectively, we have shown in a 3D culture model that endothelial cells are potent inducers of EMT in breast epithelial cells with stem cell properties. Furthermore, we demonstrate that basal-like breast cancer contains cells with an EMT phenotype, most prominently close to vascular rich areas of these tumors. We conclude that endothelial cells are potent inducers of EMT and may play a role in progression of basal-like breast cancer. PMID:21915264

Asymmetrically localized proteins stabilize basal bodies against ciliary beating forces

PubMed Central

Galati, Domenico F.

2016-01-01

Basal bodies are radially symmetric, microtubule-rich structures that nucleate and anchor motile cilia. Ciliary beating produces asymmetric mechanical forces that are resisted by basal bodies. To resist these forces, distinct regions within the basal body ultrastructure and the microtubules themselves must be stable. However, the molecular components that stabilize basal bodies remain poorly defined. Here, we determine that Fop1 functionally interacts with the established basal body stability components Bld10 and Poc1. We find that Fop1 and microtubule glutamylation incorporate into basal bodies at distinct stages of assembly, culminating in their asymmetric enrichment at specific triplet microtubule regions that are predicted to experience the greatest mechanical force from ciliary beating. Both Fop1 and microtubule glutamylation are required to stabilize basal bodies against ciliary beating forces. Our studies reveal that microtubule glutamylation and Bld10, Poc1, and Fop1 stabilize basal bodies against the forces produced by ciliary beating via distinct yet interdependent mechanisms. PMID:27807131

Loss of Dickkopf 3 Promotes the Tumorigenesis of Basal Breast Cancer

PubMed Central

Lorsy, Eva; Topuz, Aylin Sophie; Geisler, Cordelia; Stahl, Sarah; Garczyk, Stefan; von Stillfried, Saskia; Hoss, Mareike; Gluz, Oleg; Hartmann, Arndt; Knüchel, Ruth; Dahl, Edgar

2016-01-01

Dickkopf 3 (DKK3) has been associated with tumor suppression of various tumor entities including breast cancer. However, the functional impact of DKK3 on the tumorigenesis of distinct molecular breast cancer subtypes has not been considered so far. Therefore, we initiated a study analyzing the subtype-specific DKK3 expression pattern as well as its prognostic and functional impact with respect to breast cancer subtypes. Based on three independent tissue cohorts including one in silico dataset (n = 30, n = 463 and n = 791) we observed a clear down-regulation of DKK3 expression in breast cancer samples compared to healthy breast tissue controls on mRNA and protein level. Interestingly, most abundant reduction of DKK3 expression was detected in the highly aggressive basal breast cancer subtype. Analyzing a large in silico dataset comprising 3,554 cases showed that low DKK3 mRNA expression was significantly associated with reduced recurrence free survival (RFS) of luminal and basal-like breast cancer cases. Functionally, DKK3 re-expression in human breast cancer cell lines led to suppression of cell growth possibly mediated by up-regulation of apoptosis in basal-like but not in luminal-like breast cancer cell lines. Moreover, ectopic DKK3 expression in mesenchymal basal breast cancer cells resulted in partial restoration of epithelial cell morphology which was molecularly supported by higher expression of epithelial markers like E-Cadherin and down-regulation of mesenchymal markers such as Snail 1. Hence, we provide evidence that down-regulation of DKK3 especially promotes tumorigenesis of the aggressive basal breast cancer subtype. Further studies decoding the underlying molecular mechanisms of DKK3-mediated effects may help to identify novel targeted therapies for this clinically highly relevant breast cancer subtype. PMID:27467270

Metabolic Context of the Competence-Induced Checkpoint for Cell Replication in Streptococcus suis.

PubMed

Zaccaria, Edoardo; Wells, Jerry M; van Baarlen, Peter

2016-01-01

Natural genetic transformation is a transient, rapidly progressing energy-consuming process characterized by expression of the transformasome and competence-associated regulatory genes. This transient state is tightly controlled to avoid potentially adverse effects of genetic recombination on genome integrity during cell division. We investigated the global response of Streptococcus suis to exposure to the SigX competence-inducing peptide (XIP), and thus to the activation of the competence machinery, using time series analysis together with PCA analysis, gene clustering followed by heatmap visualisation, and GO enrichment analysis. We explored the possible regulatory link between metabolism and competence, and predicted the physiological adaptation of S. suis during competence induction, progression and exit using transcriptome analysis. We showed that competence development is associated with a suppression of basal metabolism, which may have consequences for the microbe's resilience to fluctuations in the environment, as competence is costly in terms of use of energy and protein translation. Furthermore our data suggest that several basal metabolic pathways are incompatible with activation of competence in S. suis. This study also showed that targeting specific pathways during the development of competence, might render S. suis more vulnerable toward novel antibiotic therapies.

Metabolic Context of the Competence-Induced Checkpoint for Cell Replication in Streptococcus suis

PubMed Central

Zaccaria, Edoardo; Wells, Jerry M.

2016-01-01

Natural genetic transformation is a transient, rapidly progressing energy-consuming process characterized by expression of the transformasome and competence-associated regulatory genes. This transient state is tightly controlled to avoid potentially adverse effects of genetic recombination on genome integrity during cell division. We investigated the global response of Streptococcus suis to exposure to the SigX competence-inducing peptide (XIP), and thus to the activation of the competence machinery, using time series analysis together with PCA analysis, gene clustering followed by heatmap visualisation, and GO enrichment analysis. We explored the possible regulatory link between metabolism and competence, and predicted the physiological adaptation of S. suis during competence induction, progression and exit using transcriptome analysis. We showed that competence development is associated with a suppression of basal metabolism, which may have consequences for the microbe's resilience to fluctuations in the environment, as competence is costly in terms of use of energy and protein translation. Furthermore our data suggest that several basal metabolic pathways are incompatible with activation of competence in S. suis. This study also showed that targeting specific pathways during the development of competence, might render S. suis more vulnerable toward novel antibiotic therapies. PMID:27149631

Basal Cells Are a Multipotent Progenitor Capable of Renewing the Bronchial Epithelium

PubMed Central

Hong, Kyung U.; Reynolds, Susan D.; Watkins, Simon; Fuchs, Elaine; Stripp, Barry R.

2004-01-01

Commitment of the pulmonary epithelium to bronchial and bronchiolar airway lineages occurs during the transition from pseudoglandular to cannalicular phases of lung development, suggesting that regional differences exist with respect to the identity of stem and progenitor cells that contribute to epithelial maintenance in adulthood. We previously defined a critical role for Clara cell secretory protein-expressing (CE) cells in renewal of bronchiolar airway epithelium following injury. Even though CE cells are also the principal progenitor for maintenance of the bronchial airway epithelium, CE cell injury is resolved through a mechanism involving recruitment of a second progenitor cell population that we now identify as a GSI-B4 reactive, cytokeratin-14-expressing basal cell. These cells exhibit multipotent differentiation capacity as assessed by analysis of cellular phenotype within clones of LacZ-tagged cells. Clones were derived from K14-expressing cells tagged in a cell-type-specific fashion by ligand-regulable Cre recombinase-mediated genomic rearrangement of the ROSA26 recombination substrate allele. We conclude that basal cells represent an alternative multipotent progenitor cell population of bronchial airways and that progenitor cell selection is dictated by the type of airway injury. PMID:14742263

Human Prostate Sphere-Forming Cells Represent a Subset of Basal Epithelial Cells Capable of Glandular Regeneration in Vivo

PubMed Central

Garraway, Isla P; Sun, Wenyi; Tran, Chau P; Perner, Sven; Zhang, Bao; Goldstein, Andrew S; Hahm, Scott A; Haider, Maahum; Head, Christian S; Reiter, Robert E; Rubin, Mark A; Witte, Owen N

2010-01-01

BACKGROUND Prostate stem/progenitor cells function in glandular development and maintenance. They may be targets for tumor initiation, so characterization of these cells may have therapeutic implications. Cells from dissociated tissues that form spheres in vitro often represent stem/progenitor cells. A subset of human prostate cells that form prostaspheres were evaluated for self-renewal and tissue regeneration capability in the present study. METHODS Prostaspheres were generated from 59 prostatectomy specimens. Lineage marker expression and TMPRSS-ERG status was determined via immunohistochemistry and fluorescence in situ hybridization (FISH). Subpopulations of prostate epithelial cells were isolated by cell sorting and interrogated for sphere-forming activity. Tissue regeneration potential was assessed by combining sphere-forming cells with rat urogenital sinus mesenchyme (rUGSM) subcutaneously in immunocompromised mice. RESULTS Prostate tissue specimens were heterogeneous, containing both benign and malignant (Gleason 3–5) glands. TMPRSS-ERG fusion was found in approximately 70% of cancers examined. Prostaspheres developed from single cells at a variable rate (0.5–4%) and could be serially passaged. A basal phenotype (CD44+CD49f+CK5+p63+CK8−AR−PSA−) was observed among sphere-forming cells. Subpopulations of prostate cells expressing tumor-associated calcium signal transducer 2 (Trop2), CD44, and CD49f preferentially formed spheres. In vivo implantation of sphere-forming cells and rUGSM regenerated tubular structures containing discreet basal and luminal layers. The TMPRSS-ERG fusion was absent in prostaspheres derived from fusion-positive tumor tissue, suggesting a survival/growth advantage of benign prostate epithelial cells. CONCLUSION Human prostate sphere-forming cells self-renew, have tissue regeneration capability, and represent a subpopulation of basal cells. Prostate 70: 491–501, 2010. © 2009 Wiley-Liss, Inc. PMID:19938015

Basal Immunoglobulin Signaling Actively Maintains Developmental Stage in Immature B Cells

PubMed Central

Tze, Lina E; Schram, Brian R; Lam, Kong-Peng; Hogquist, Kristin A; Hippen, Keli L; Liu, Jiabin; Shinton, Susan A; Otipoby, Kevin L; Rodine, Peter R; Vegoe, Amanda L; Kraus, Manfred; Hardy, Richard R; Schlissel, Mark S; Rajewsky, Klaus

2005-01-01

In developing B lymphocytes, a successful V(D)J heavy chain (HC) immunoglobulin (Ig) rearrangement establishes HC allelic exclusion and signals pro-B cells to advance in development to the pre-B stage. A subsequent functional light chain (LC) rearrangement then results in the surface expression of IgM at the immature B cell stage. Here we show that interruption of basal IgM signaling in immature B cells, either by the inducible deletion of surface Ig via Cre-mediated excision or by incubating cells with the tyrosine kinase inhibitor herbimycin A or the phosphatidylinositol 3-kinase inhibitor wortmannin, led to a striking “back-differentiation” of cells to an earlier stage in B cell development, characterized by the expression of pro-B cell genes. Cells undergoing this reversal in development also showed evidence of new LC gene rearrangements, suggesting an important role for basal Ig signaling in the maintenance of LC allelic exclusion. These studies identify a previously unappreciated level of plasticity in the B cell developmental program, and have important implications for our understanding of central tolerance mechanisms. PMID:15752064

Comparative Morphology of Sulfur Mustard Effects in the Hairless Guinea Pig and a Human Skin Equivalent

DTIC Science & Technology

1993-01-01

guinea pig model (HD-HGP). HSE samples were exposed to 10 micro l HD vapor for 8 min and harvested at selected times up to 24 h. Skin sites of HGP were exposed to the same vapor dose or to 2.0 micro l HD for 30 min and collected at 12 and 24 h. In both models, basal cells of the stratum germinativum were selectively affected. The HD-HSE study revealed that basal cell changes began 3 to 6 h following exposure. These early cellular included an acantholysis of some basal cells with widening of intercellular spaces, disruption of desmosomal attachments, nuclear pyknosis,

Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer

DTIC Science & Technology

2012-10-01

this collaboration. BODY: Generate tumor lysates pooled from BC cell lines of each major subtype (luminal, HER2+, basal) [Task 4a] Given the...presented epitopes. The IEDB provides downloadable command-line driven tools for the prediction of input sequence binding affinity to MHC class I or class ...69 9 Epirubicin 317 nM 29 16 35 10 Etoposide 4 µM 60 43 48 11 Fascaplysin 167 nM 22 -19 -14 12 Ibandronate 63 µM -34 -56 -52 13 ICRF-193 11 µM

Morphological elucidation of basal ganglia circuits contributing reward prediction

PubMed Central

Fujiyama, Fumino; Takahashi, Susumu; Karube, Fuyuki

2015-01-01

Electrophysiological studies in monkeys have shown that dopaminergic neurons respond to the reward prediction error. In addition, striatal neurons alter their responsiveness to cortical or thalamic inputs in response to the dopamine signal, via the mechanism of dopamine-regulated synaptic plasticity. These findings have led to the hypothesis that the striatum exhibits synaptic plasticity under the influence of the reward prediction error and conduct reinforcement learning throughout the basal ganglia circuits. The reinforcement learning model is useful; however, the mechanism by which such a process emerges in the basal ganglia needs to be anatomically explained. The actor–critic model has been previously proposed and extended by the existence of role sharing within the striatum, focusing on the striosome/matrix compartments. However, this hypothesis has been difficult to confirm morphologically, partly because of the complex structure of the striosome/matrix compartments. Here, we review recent morphological studies that elucidate the input/output organization of the striatal compartments. PMID:25698913

Immunohistochemical expression of CK7, CK5/6, CK19, and p63 in Warthin tumor.

PubMed

Dăguci, Luminiţa; Stepan, A; Mercuţ, Veronica; Dăguci, C; Bătăiosu, Marilena; Florescu, Alma

2012-01-01

Our study included a number of 24 cases with Warthin tumor, diagnosed between 2007-2011, which were analyzed in terms of clinical, histopathological and immunohistochemistry point of view, using CK7, CK5/6, CK19, and p63 antibodies. Warthin tumor is most often a tumor with a slow evolution, painless, usually affecting males (M/F 3.2/1) in the seventh decade of life. Histopathologically, it is distinguished the predominance of the typical forms of the tumor, with a balanced ratio epithelium/stroma. The immunostaining for CK7 showed positivity in all the investigated cases both in the columnar luminal cells and basal cells. The immunostaining for CK5/6 was positive in all the investigated cases in bilayer epithelial basal cells, both in the structure of the cysts and the papillae. In the case of the immunostaining for p63 we noticed limited nuclear positivity in the basal cells, while the columnar cells' nucleus were negative. The immunohistochemical study of the bilayer epithelial component of Warthin tumor showed different immunstaining of the two types of epithelia, the oncocytary columnar and the basal on, similar to those found in the salivary gland ducts.

Demonstration of intermediate cells during human prostate epithelial differentiation in situ and in vitro using triple-staining confocal scanning microscopy.

PubMed

van Leenders, G; Dijkman, H; Hulsbergen-van de Kaa, C; Ruiter, D; Schalken, J

2000-08-01

In human prostate epithelium, morphologically basal and luminal cells can be discriminated. The basal cell layer that putatively contains progenitor cells of the secretory epithelium is characterized by the expression of keratins (K) 5 and 14. Luminal cells represent the secretory compartment of the epithelium and express K8 and 18. We developed a technique for the simultaneous analysis of K5, 14, and 18 to identify intermediate cell stages in the prostate epithelium and to study the dynamic aspects of its differentiation in vitro. Nonmalignant prostate tissue and primary epithelial cultures were immunohistochemically characterized using triple staining with antibodies for K5, K14, and K18. Antibodies for K18 and K5 were conjugated directly with fluorochromes Alexa 488 and 546. K14 was visualized indirectly with streptavidin-Cy5. Keratin expression was analyzed by confocal scanning microscopy. The occurrence of exocrine and neuroendocrine differentiation in culture was determined via antibodies to prostate-specific antigen (PSA), chromogranin A, and serotonin. We found that basal cells expressed either K5(++)/14(++)/18+ or K5(++)/18+. The majority of luminal cells expressed K18(++), but colocalization of K5+/18(++) were recognized. Epithelial monolayer cultures predominantly revealed the basal cell phenotype K5(++)/14(++)/18+, whereas intermediate subpopulations expressing K5+/14+/18(++) and K5+/18(++) were also identified. On confluence, differentiation was induced as multicellular gland-like buds, and extensions became evident on top of the monolayer. These structures were composed of K18(++)- and K5+/18(+)-positive cell clusters surrounded by phenotypically basal cells. Few multicellular structures and cells in the monolayer showed exocrine differentiation (PSA+), but expression of chromogranin A and serotonin was absent. We conclude that simultaneous evaluation of keratin expression is useful for analyzing epithelial differentiation in the prostate. During this process, putative stem cells phenotypically resembling K5(++)/14(++)/18+ differentiate toward luminal cells (K18(++)) via intermediate cell stages, as identified by up-regulation of K18 and down-regulation of K5 and 14.

The influence of prostatic anatomy and neurotrophins on basal prostate epithelial progenitor cells.

PubMed

Höfner, Thomas; Klein, Corinna; Eisen, Christian; Rigo-Watermeier, Teresa; Haferkamp, Axel; Trumpp, Andreas; Sprick, Martin R

2016-01-01

Based on findings of surface marker, protein screens as well as the postulated near-urethral location of the prostate stem cell niche, we were interested whether androgen ablation, distinct anatomic regions within the prostate or neurotrophins have an influence on basal prostate epithelial progenitor cells (PESCs). Microdissection of the prostate, enzymatic digestion, and preparation of single cells was performed from murine and human prostates. Adult PESC marker expressions were compared between a group of C57BL/6 mice and a separate group of castrated C57BL/6 mice. Surface markers CD13/CD271 on human prostate epithelial progenitor cells were evaluated by FACS analyses in cells cultured under novel stem cell conditions. The effect of neurotrophins NGF, NT3, and BDNF were evaluated with respect to their influence on proliferation and activation of human basal PESCs in vitro. We demonstrate the highest percentage of CD49f+ and Trop2+ expressing cells in the urethra near prostatic regions of WT mice (Trop2+ proximal: 10% vs. distal to the urethra: 3%, P < 0.001). While a marked increase of Trop2 expressing cells can be measured both in the proximal and distal prostatic regions after castration, the most prominent increase in Trop2+ cells can be measured in the prostatic tissue distant to the urethra. Furthermore, we demonstrate that the proportion of syndecan-1 expressing cells greatly increases in the regions proximal to the urethra after castration (WT: 5% vs. castrated: 40%). We identified heterogeneous CD13 and nerve growth factor receptor (p75(NGFR), CD271) expression on CD49f(+)/TROP2(high) human basal PESCs. Addition of the neurotrophins NT3, BDNF, and NGF to the stem cell media led to a marked temporary increase in the proliferation of human basal PESCs. Our results in mice support the model, in which the proximal urethral region contains the prostate stem cell niche while a stronger androgen-dependent regulation of adult prostate stem cells can be found in the peripheral prostatic tissue. Neutrophin signaling via nerve growth factor receptor is possibly involved in human prostate stem cell homeostasis. © 2015 Wiley Periodicals, Inc.

Further localization of the gene for nevoid basal cell carcinoma syndrome (NBCCS) in 15 Australasian families: Linkage and loss of heterozygosity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chenevix-Trench, G.; Wicking, C.; Berkman, J.

Nevoid basal cell carcinoma syndrome (NBCCS; basal cell nevus syndrome or Gorlin syndrome) is a cancer-predisposition syndrome characterized by multiple basal cell carcinomas (BCCs) and diverse developmental defects. The gene for NBCCS has been mapped to 9q23.1-q31 in North Americal and European families. In addition, loss of heterozygosity (LOH) for genetic markers in this region has been detected in sporadic BCCs, indicating that the NBCCs gene is probably a tumor-suppressor gene. In this study the authors have determined that the NBCCS gene is also linked to this region in Australasian pedigrees and that there is no significant evidence of heterogeneity.more » They have defined the localization of the gene by multipoint and haplotype analysis of 15 families, using four microsatellite markers. LOH at these loci was detected in 50% of sporadic BCCs, a rate that is significantly higher than that in other skin lesions used as controls. 21 refs., 3 figs., 2 tabs.« less

Evaluation of Basal Serum or Plasma Cortisol Concentrations for the Diagnosis of Hypoadrenocorticism in Dogs.

PubMed

Gold, A J; Langlois, D K; Refsal, K R

2016-11-01

Previous studies that included limited numbers of affected dogs have suggested basal cortisol concentrations ≤55 nmol/L (2 μg/dL) are sensitive, but nonspecific, for a diagnosis of hypoadrenocorticism. A detailed assessment of the diagnostic utility of basal cortisol concentrations is warranted. To evaluate the utility of basal cortisol concentrations for the diagnosis of hypoadrenocorticism in a large number of dogs, including those with and without serum electrolyte abnormalities. Five hundred and twenty-two dogs, including 163 dogs with hypoadrenocorticism, 351 dogs with nonadrenal gland illness, and 8 dogs with equivocal results. Retrospective study. Basal and post-ACTH cortisol concentrations and sodium and potassium concentrations were collected from medical records. A receiver operating characteristic (ROC) curve was constructed for basal cortisol concentrations by standard methodologies. Sensitivity, specificity, and predictive values were determined for various cut-points. The area under the ROC curve was 0.988 and was similarly excellent regardless of serum electrolyte concentrations. At the most discriminatory cut-point of 22 nmol/L (0.8 μg/dL), sensitivity and specificity were 96.9 and 95.7%, respectively. A basal cortisol concentration of ≤55 nmol/L (2 μg/dL) resulted in a sensitivity of 99.4%. Conversely, a basal cortisol concentration of ≤5.5 nmol/L (0.19 μg/dL) resulted in a specificity of 99.1%. Similar to findings in previous studies, basal cortisol concentrations >55 nmol/L (2 μg/dL) are useful in excluding a diagnosis of hypoadrenocorticism. Interestingly, excellent specificities and positive predictive values were observed at lower cut-point cortisol concentrations. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Seasonal thermoregulatory responses in mammals.

PubMed

Lovegrove, Barry G

2005-05-01

This study examined the proportional seasonal winter adjustments of total and mass-specific basal power (watts and watts g-1, respectively), thermal conductance (watts g-1 degrees C-1), non-shivering thermogenesis capacity (ratio of NST/basal power), body temperature ( degrees C), and body mass (g) of mammals. The responses are best summarized for three different body size classes; small mammals (<100 g), intermediate-sized mammals (0.1-10 kg), and large mammals (>10 kg). The principal adjustments of the small mammals center on energy conservation, especially the Dehnel Effect, the winter reduction in body size of as much as 50%, accompanied by reductions in mass-specific basal power. On average, these reductions reduce the total basal power approximately in direct proportion to the mass reductions. Reductions in mass-specific basal power are matched by concomitant reductions in conductance to maintain the setpoint body temperature during winter. The overall thermoregulatory adjustments in small mammals serve to (a) lower overall winter power consumption, (b) maintain the setpoint body temperature, and (c) lower the lower critical limit of thermoneutrality and hence thermoregulatory costs. In intermediate-size mammals, the seasonal response is centered more on increasing thermogenic capacity by increasing basal power and NST capacity, accompanied by predictable and large reductions in conductance. The Dehnel effect is negligible. Very large mammals undergo the largest reductions in total and mass-specific basal power and conductance. However, there are too few data to resolve whether the reductions in total basal power can be attributed to the Dehnel effect, because the moderate decreases in body mass may also be caused by nutritional stress. Apart from the seasonal changes in basal power, these observations are consistent with the predictions of Heldmaier's seasonal acclimatization model.

MDCK cells are capable of water secretion and reabsorption in response to changes in the ionic environment.

PubMed

Capra, Janne P; Eskelinen, Sinikka M

2017-01-01

A prerequisite for tissue electrolyte homeostasis is highly regulated ion and water transport through kidney or intestinal epithelia. In the present work, we monitored changes in the cell and luminal volumes of type II Madin-Darby canine kidney (MDCK) cells grown in a 3D environment in response to drugs, or to changes in the composition of the basal extracellular fluid. Using fluorescent markers and high-resolution spinning disc confocal microscopy, we could show that lack of sodium and potassium ions in the basal fluid (tetramethylammonium chloride (TMACl) buffer) induces a rapid increase in the cell and luminal volumes. This transepithelial water flow could be regulated by inhibitors and agonists of chloride channels. Hence, the driving force for the transepithelial water flow is chloride secretion, stimulated by hyperpolarization. Chloride ion depletion of the basal fluid (using sodium gluconate buffer) induces a strong reduction in the lumen size, indicating reabsorption of water from the lumen to the basal side. Lumen size also decreased following depolarization of the cell interior by rendering the membrane permeable to potassium. Hence, MDCK cells are capable of both absorption and secretion of chloride ions and water; negative potential within the lumen supports secretion, while depolarizing conditions promote reabsorption.

Apical and basal epitheliomuscular F-actin dynamics during Hydra bud evagination

PubMed Central

Aufschnaiter, Roland; Wedlich-Söldner, Roland; Zhang, Xiaoming

2017-01-01

ABSTRACT Bending of 2D cell sheets is a fundamental morphogenetic mechanism during animal development and reproduction. A critical player driving cell shape during tissue bending is the actin cytoskeleton. Much of our current knowledge about actin dynamics in whole organisms stems from studies of embryonic development in bilaterian model organisms. Here, we have analyzed actin-based processes during asexual bud evagination in the simple metazoan Hydra. We created transgenic Hydra strains stably expressing the actin marker Lifeact-GFP in either ectodermal or endodermal epitheliomuscular cells. We then combined live imaging with conventional phalloidin staining to directly follow actin reorganization. Bending of the Hydra epithelial double layer is initiated by a group of epitheliomuscular cells in the endodermal layer. These cells shorten their apical-basal axis and arrange their basal muscle processes in a circular configuration. We propose that this rearrangement generates the initial forces to bend the endoderm towards the ectoderm. Convergent tissue movement in both epithelial layers towards the centre of evagination then leads to elongation and extension of the bud along its new body axis. Tissue movement into the bud is associated with lateral intercalation of epithelial cells, remodelling of apical septate junctions, and rearrangement of basal muscle processes. The work presented here extends the analysis of morphogenetic mechanisms beyond embryonic tissues of model bilaterians. PMID:28630355

A Cellular Automaton / Finite Element model for predicting grain texture development in galvanized coatings

NASA Astrophysics Data System (ADS)

Guillemot, G.; Avettand-Fènoël, M.-N.; Iosta, A.; Foct, J.

2011-01-01

Hot-dipping galvanizing process is a widely used and efficient way to protect steel from corrosion. We propose to master the microstructure of zinc grains by investigating the relevant process parameters. In order to improve the texture of this coating, we model grain nucleation and growth processes and simulate the zinc solid phase development. A coupling scheme model has been applied with this aim. This model improves a previous two-dimensional model of the solidification process. It couples a cellular automaton (CA) approach and a finite element (FE) method. CA grid and FE mesh are superimposed on the same domain. The grain development is simulated at the micro-scale based on the CA grid. A nucleation law is defined using a Gaussian probability and a random set of nucleating cells. A crystallographic orientation is defined for each one with a choice of Euler's angle (Ψ,θ,φ). A small growing shape is then associated to each cell in the mushy domain and a dendrite tip kinetics is defined using the model of Kurz [2]. The six directions of basal plane and the two perpendicular directions develop in each mushy cell. During each time step, cell temperature and solid fraction are then determined at micro-scale using the enthalpy conservation relation and variations are reassigned at macro-scale. This coupling scheme model enables to simulate the three-dimensional growing kinetics of the zinc grain in a two-dimensional approach. Grain structure evolutions for various cooling times have been simulated. Final grain structure has been compared to EBSD measurements. We show that the preferentially growth of dendrite arms in the basal plane of zinc grains is correctly predicted. The described coupling scheme model could be applied for simulated other product or manufacturing processes. It constitutes an approach gathering both micro and macro scale models.

Heterogeneous fates and dynamic rearrangement of regenerative epidermis-derived cells during zebrafish fin regeneration.

PubMed

Shibata, Eri; Ando, Kazunori; Murase, Emiko; Kawakami, Atsushi

2018-04-13

The regenerative epidermis (RE) is a specialized tissue that plays an essential role in tissue regeneration. However, the fate of the RE during and after regeneration is unknown. In this study, we performed Cre- loxP -mediated cell fate tracking and revealed the fates of a major population of the RE cells that express fibronectin 1b ( fn1b ) during zebrafish fin regeneration. Our study showed that these RE cells are mainly recruited from the inter-ray epidermis, and that they follow heterogeneous cell fates. Early recruited cells contribute to initial wound healing and soon disappear by apoptosis, while the later recruited cells contribute to the regenerated epidermis. Intriguingly, many of these cells are also expelled from the regenerated tissue by a dynamic caudal movement of the epidermis over time, and in turn the loss of epidermal cells is replenished by a global self-replication of basal and suprabasal cells in fin. De-differentiation of non-basal epidermal cells into the basal epidermal cells did not occur during regeneration. Overall, our study reveals the heterogeneous fates of RE cells and a dynamic rearrangement of the epidermis during and after regeneration. © 2018. Published by The Company of Biologists Ltd.

Protein profiling of single epidermal cell types from Arabidopsis thaliana using surface-enhanced laser desorption and ionization technology.

PubMed

Ebert, Berit; Melle, Christian; Lieckfeldt, Elke; Zöller, Daniela; von Eggeling, Ferdinand; Fisahn, Joachim

2008-08-25

Here, we describe a novel approach for investigating differential protein expression within three epidermal cell types. In particular, 3000 single pavement, basal, and trichome cells from leaves of Arabidopsis thaliana were harvested by glass micro-capillaries. Subsequently, these single cell samples were joined to form pools of 100 individual cells and analyzed using the ProteinChip technology; SELDI: surface-enhanced laser desorption and ionization. As a result, numerous protein signals that were differentially expressed in the three epidermal cell types could be detected. One of these proteins was characterized by tryptical digestion and subsequent identification via tandem quadrupole-time of flight (Q-TOF) mass spectrometry. Down regulation of this sequenced small subunit precursor of ribulose-1,5 bisphosphate carboxylase(C) oxygenase(O) (RuBisCo) in trichome and basal cells indicates the sink status of these cell types that are located on the surface of A. thaliana source leaves. Based on the obtained protein profiles, we suggest a close functional relationship between basal and trichome cells at the protein level.

Progression of urothelial carcinoma in situ of the urinary bladder: a switch from luminal to basal phenotype and related therapeutic implications.

PubMed

Barth, Isabella; Schneider, Ursula; Grimm, Tobias; Karl, Alexander; Horst, David; Gaisa, Nadine T; Knüchel, Ruth; Garczyk, Stefan

2018-05-01

The stratification of bladder cancer into luminal and basal tumors has recently been introduced as a novel prognostic system in patient cohorts of muscle-invasive bladder cancer or high-grade papillary carcinomas. Using a representative immunohistochemistry panel, we analyzed luminal and basal marker expression in a large case series (n = 156) of urothelial carcinoma in situ (CIS), a precancerous lesion that frequently progresses to muscle-invasive disease. The majority of CIS cases was characterized by a positivity for luminal markers (aberrant cytokeratin (CK) 20 85% (132/156), GATA3 median Remmele score (score of staining intensity (0-3) multiplied with percentage of positive cells (0-4)): 12, estrogen receptor (ER) β Remmele score > 2: 88% (138/156), human epidermal growth factor receptor 2 (Her2) Dako score 3+ 32% (50/156), Her2 Dako score 2+ 33% (51/156)), and marginal expression of basal markers (CK5/6+ 2% (3/156), CK14+ 1% (2/156)). To further investigate phenotypic stability during disease progression, we compared 48 pairs of CIS and invasive tumors from the same biopsy. A highly significant loss of luminal marker expression (p < 0.001) was observed in the course of progression whereas an increase of basal marker expression (p < 0.01) was noted in the invasive compartment. Importantly, 91% of CIS cases demonstrated a positivity for at least one of the two predictive markers Her2 and ERβ, indicating that the analysis of Her2 and ERβ may help to identify CIS-patient subgroups prone to more efficient targeted treatment strategies. Larger prospective and biomarker-embedded clinical trials are needed to confirm and validate our preliminary findings.

Identification of heparin-binding EGF-like growth factor as a target in intercellular regulation of epidermal basal cell growth by suprabasal retinoic acid receptors.

PubMed Central

Xiao, J H; Feng, X; Di, W; Peng, Z H; Li, L A; Chambon, P; Voorhees, J J

1999-01-01

The role of retinoic acid receptors (RARs) in intercellular regulation of cell growth was assessed by targeting a dominant-negative RARalpha mutant (dnRARalpha) to differentiated suprabasal cells of mouse epidermis. dnRARalpha lacks transcriptional activation but not DNA-binding and receptor dimerization functions. Analysis of transgenic mice revealed that dnRARalpha dose-dependently impaired induction of basal cell proliferation and epidermal hyperplasia by all-trans RA (tRA). dnRARalpha formed heterodimers with endogenous retinoid X receptor-alpha (RXRalpha) over RA response elements in competition with remaining endogenous RARgamma-RXRalpha heterodimers, and dose-dependently impaired retinoid-dependent gene transcription. To identify genes regulated by retinoid receptors and involved in cell growth control, we analyzed the retinoid effects on expression of the epidermal growth factor (EGF) receptor, EGF, transforming growth factor-alpha, heparin-binding EGF-like growth factor (HB-EGF) and amphiregulin genes. In normal epidermis, tRA rapidly and selectively induced expression of HB-EGF but not the others. This induction occurred exclusively in suprabasal cells. In transgenic epidermis, dnRARalpha dose-dependently inhibited tRA induction of suprabasal HB-EGF and subsequent basal cell hyperproliferation. Together, our observations suggest that retinoid receptor heterodimers located in differentiated suprabasal cells mediate retinoid induction of HB-EGF, which in turn stimulates basal cell growth via intercellular signaling. These events may underlie retinoid action in epidermal regeneration during wound healing. PMID:10075925

Tetrahymena Poc1 ensures proper intertriplet microtubule linkages to maintain basal body integrity

PubMed Central

Meehl, Janet B.; Bayless, Brian A.; Giddings, Thomas H.; Pearson, Chad G.; Winey, Mark

2016-01-01

Basal bodies comprise nine symmetric triplet microtubules that anchor forces produced by the asymmetric beat pattern of motile cilia. The ciliopathy protein Poc1 stabilizes basal bodies through an unknown mechanism. In poc1∆ cells, electron tomography reveals subtle defects in the organization of intertriplet linkers (A-C linkers) that connect adjacent triplet microtubules. Complete triplet microtubules are lost preferentially near the posterior face of the basal body. Basal bodies that are missing triplets likely remain competent to assemble new basal bodies with nine triplet microtubules, suggesting that the mother basal body microtubule structure does not template the daughter. Our data indicate that Poc1 stabilizes basal body triplet microtubules through linkers between neighboring triplets. Without this stabilization, specific triplet microtubules within the basal body are more susceptible to loss, probably due to force distribution within the basal body during ciliary beating. This work provides insights into how the ciliopathy protein Poc1 maintains basal body integrity. PMID:27251062

Genotoxic Exposure during Juvenile Growth of Mammary Gland Depletes Stem Cell Activity and Inhibits Wnt Signaling

PubMed Central

Klos, Kristine S.; Kim, Soyoung; Alexander, Caroline M.

2012-01-01

Various types of somatic stem cell have been tested for their response to genotoxic exposure, since these cells are likely to be important to regeneration, aging and cancer. In this study, we evaluated the response of mammary stem cells to genotoxic exposure during ductal growth in juveniles. Exposure to the polycyclic aromatic hydrocarbon (DMBA; 7,12 dimethylbenz[a]anthracene) had no gross effect on outgrowth and morphogenesis of the ductal tree, or upon lobuloalveolar growth during pregnancy. However, by fat pad assay, we found that mammary stem cell activity was reduced by 80% in glands from adults that were exposed to genotoxins as juveniles. The associated basal cell lineage was depleted. Both basal and luminal cells showed a robust response to genotoxic exposure (including γH2AX phosphorylation, pS15p53 and pT68Chk2), with durable hyperproliferation, but little cytotoxicity. Since the phenotype of these glands (low basal cell fraction, low stem cell activity) phenocopies mammary glands with loss of function for Wnt signaling, we measured Wnt signaling in genotoxin-exposed glands, and found a durable reduction in the activation of the canonical signaling Wnt receptors, Lrp5/6. Furthermore, when mammary epithelial cells were treated with Wnt3a, DMBA exposure reduced the basal cell population and Lrp activation was ablated. We conclude that during active ductal growth, Wnt-dependent mammary stem cells are sensitized to cell death by genotoxin exposure. Our conclusion may be important for other tissues, since all solid tumor stem cell activities have been shown to be Wnt-dependent to date. PMID:23185480

Niche induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool

PubMed Central

Mesa, Kailin R.; Rompolas, Panteleimon; Zito, Giovanni; Myung, Peggy; Sun, Thomas Yang; Brown, Samara; Gonzalez, David; Blagoev, Krastan B.; Haberman, Ann M.; Greco, Valentina

2015-01-01

Summary Tissue homeostasis is achieved through a balance of cell production (growth) and elimination (regression)1,2. Contrary to tissue growth, the cells and molecular signals required for tissue regression remain unknown. To investigate physiological tissue regression, we use the mouse hair follicle, which cycles stereotypically between phases of growth and regression while maintaining a pool of stem cells to perpetuate tissue regeneration3. Here we show by intravital microscopy in live mice4–6 that the regression phase eliminates the majority of the epithelial cells by two distinct mechanisms: terminal differentiation of suprabasal cells and a spatial gradient of apoptosis of basal cells. Furthermore, we demonstrate that basal epithelial cells collectively act as phagocytes to clear dying epithelial neighbors. Through cellular and genetic ablation we show that epithelial cell death is extrinsically induced through TGFβ activation and mesenchymal crosstalk. Strikingly, our data show that regression acts to reduce the stem cell pool as inhibition of regression results in excess basal epithelial cells with regenerative abilities. This study identifies the cellular behaviors and molecular mechanisms of regression that counterbalance growth to maintain tissue homeostasis. PMID:25849774

Targeting IL13Ralpha2 activates STAT6-TP63 pathway to suppress breast cancer lung metastasis.

PubMed

Papageorgis, Panagiotis; Ozturk, Sait; Lambert, Arthur W; Neophytou, Christiana M; Tzatsos, Alexandros; Wong, Chen K; Thiagalingam, Sam; Constantinou, Andreas I

2015-07-25

Basal-like breast cancer (BLBC) is an aggressive subtype often characterized by distant metastasis, poor patient prognosis, and limited treatment options. Therefore, the discovery of alternative targets to restrain its metastatic potential is urgently needed. In this study, we aimed to identify novel genes that drive metastasis of BLBC and to elucidate the underlying mechanisms of action. An unbiased approach using gene expression profiling of a BLBC progression model and in silico leveraging of pre-existing tumor transcriptomes were used to uncover metastasis-promoting genes. Lentiviral-mediated knockdown of interleukin-13 receptor alpha 2 (IL13Ralpha2) coupled with whole-body in vivo bioluminescence imaging was performed to assess its role in regulating breast cancer tumor growth and lung metastasis. Gene expression microarray analysis was followed by in vitro validation and cell migration assays to elucidate the downstream molecular pathways involved in this process. We found that overexpression of the decoy receptor IL13Ralpha2 is significantly enriched in basal compared with luminal primary breast tumors as well as in a subset of metastatic basal-B breast cancer cells. Importantly, breast cancer patients with high-grade tumors and increased IL13Ralpha2 levels had significantly worse prognosis for metastasis-free survival compared with patients with low expression. Depletion of IL13Ralpha2 in metastatic breast cancer cells modestly delayed primary tumor growth but dramatically suppressed lung metastasis in vivo. Furthermore, IL13Ralpha2 silencing was associated with enhanced IL-13-mediated phosphorylation of signal transducer and activator of transcription 6 (STAT6) and impaired migratory ability of metastatic breast cancer cells. Interestingly, genome-wide transcriptional analysis revealed that IL13Ralpha2 knockdown and IL-13 treatment cooperatively upregulated the metastasis suppressor tumor protein 63 (TP63) in a STAT6-dependent manner. These observations are consistent with increased metastasis-free survival of breast cancer patients with high levels of TP63 and STAT6 expression and suggest that the STAT6-TP63 pathway could be involved in impairing metastatic dissemination of breast cancer cells to the lungs. Our findings indicate that IL13Ralpha2 could be used as a promising biomarker to predict patient outcome and provide a rationale for assessing the efficacy of anti-IL13Ralpha2 therapies in a subset of highly aggressive basal-like breast tumors as a strategy to prevent metastatic disease.

Disparate effects of non-steroidal anti-inflammatory drugs on apoptosis in guinea-pig gastric mucous cells: inhibition of basal apoptosis by diclofenac

PubMed Central

Ashton, Miranda; Hanson, Peter J

2002-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) induce apoptosis in gastrointestinal cancer cell lines. Similar actions on normal gastric epithelial cells could contribute to NSAID gastropathy. The present work therefore compared the actions of diclofenac, ibuprofen, indomethacin, and the cyclo-oxygenase-2 selective inhibitor, NS-398, on a primary culture of guinea-pig gastric mucous epithelial cells. Cell number was assessed by staining with crystal violet. Apoptotic activity was determined by condensation and fragmentation of nuclei and by assay of caspase-3-like activity. Necrosis was evaluated from release of cellular enzymes. Ibuprofen (250 μM for 24 h) promoted cell loss, and apoptosis, under both basal conditions and when apoptosis was increased by 25 μM N-Hexanoyl-D-sphingosine (C6-ceramide). Diclofenac (250 μM for 24 h) reduced the proportion of apoptotic nuclei from 5.2 to 2.1%, and caused inhibition of caspase-3-like activity, without causing necrosis under basal conditions. No such reduction in apoptotic activity was evident in the presence of 25 μM C6-ceramide. The inhibitory effect of diclofenac on basal caspase-3-like activity was also exhibited by the structurally similar mefenamic and flufenamic acids (1–250 μM), but not by niflumic acid. Inhibition of superoxide production by the cells increased caspase-3-like activity, but the inhibitory action of diclofenac on caspase activity remained. Diclofenac did not affect superoxide production. Diclofenac inhibited caspase-3-like activity in cell homogenates and also inhibited human recombinant caspase-3. In conclusion, NSAIDs vary in their effect on apoptotic activity in a primary culture of guinea-pig gastric mucous epithelial cells, and the inhibitory effect of diclofenac on basal apoptosis could involve an action on caspase activity. PMID:11815376

Radon induced hyperplasia: effective adaptation reducing the local doses in the bronchial epithelium.

PubMed

Madas, Balázs G

2016-09-01

There is experimental and histological evidence that chronic irritation and cell death may cause hyperplasia in the exposed tissue. As the heterogeneous deposition of inhaled radon progeny results in high local doses at the peak of the bronchial bifurcations, it was proposed earlier that hyperplasia occurs in these deposition hot spots upon chronic radon exposure. The objective of the present study is to quantify how the induction of basal cell hyperplasia modulates the microdosimetric consequences of a given radon exposure. For this purpose, computational epithelium models were constructed with spherical cell nuclei of six different cell types based on histological data. Basal cell hyperplasia was modelled by epithelium models with additional basal cells and increased epithelium thickness. Microdosimetry for alpha-particles was performed by an own-developed Monte-Carlo code. Results show that the average tissue dose, and the average hit number and dose of basal cells decrease by the increase of the measure of hyperplasia. Hit and dose distribution reveal that the induction of hyperplasia may result in a basal cell pool which is shielded from alpha-radiation. It highlights that the exposure history affects the microdosimetric consequences of a present exposure, while the biological and health effects may also depend on previous exposures. The induction of hyperplasia can be considered as a radioadaptive response at the tissue level. Such an adaptation of the tissue challenges the validity of the application of the dose and dose rate effectiveness factor from a mechanistic point of view. As the location of radiosensitive target cells may change due to previous exposures, dosimetry models considering the tissue geometry characteristic of normal conditions may be inappropriate for dose estimation in case of protracted exposures. As internal exposures are frequently chronic, such changes in tissue geometry may be highly relevant for other incorporated radionuclides.

In vivo examination of the cortical cytoskeleton in multiciliated cells using electron tomography.

PubMed

Clare, Daniel K; Dumoux, Maud; Delacour, Delphine

2015-01-01

Multiciliated cells are characterized by coordinated arrays of motile cilia. In the respiratory tract, the maintenance of this array is essential to ensure proper ciliary and mucus clearance. The establishment and the maintenance of the ciliary set are mediated by the correct positioning of basal bodies at the cell cortex. While microtubule and actin cytoskeletons have been reported to regulate basal body lattices, an understanding of their detailed organization was missing until recently. Here, we describe how electron tomography can highlight the arrangement of the cytoskeletal networks and their interplay with basal bodies in ciliated cells in their tissular environment. Thanks to this approach, information in fine detail on large parts of the cell, dense in organelles, is provided. In combination with other approaches, such as transgenic animal models, electron tomography constitutes a powerful technique giving an overview of tissues and cells concomitantly with acquisition of three-dimensional detail. Copyright © 2015 Elsevier Inc. All rights reserved.

A local basal area adjustment for crown width prediction

Treesearch

Don C. Bragg

2001-01-01

Nonlinear crown width regressive equations were developed for 24 species common to the upper Lake States of Michigan, Minnesota, and Wisconsin. Of the species surveyed, 15 produced statistically significant (P 0.05) local basal area effect coefficients showing a reduction in crown...

Defined Conditions for the Isolation and Expansion of Basal Prostate Progenitor Cells of Mouse and Human Origin

PubMed Central

Höfner, Thomas; Eisen, Christian; Klein, Corinna; Rigo-Watermeier, Teresa; Goeppinger, Stephan M.; Jauch, Anna; Schoell, Brigitte; Vogel, Vanessa; Noll, Elisa; Weichert, Wilko; Baccelli, Irène; Schillert, Anja; Wagner, Steve; Pahernik, Sascha; Sprick, Martin R.; Trumpp, Andreas

2015-01-01

Summary Methods to isolate and culture primary prostate epithelial stem/progenitor cells (PESCs) have proven difficult and ineffective. Here, we present a method to grow and expand both murine and human basal PESCs long term in serum- and feeder-free conditions. The method enriches for adherent mouse basal PESCs with a Lin−SCA-1+CD49f+TROP2high phenotype. Progesterone and sodium selenite are additionally required for the growth of human Lin−CD49f+TROP2high PESCs. The gene-expression profiles of expanded basal PESCs show similarities to ESCs, and NF-kB function is critical for epithelial differentiation of sphere-cultured PESCs. When transplanted in combination with urogenital sinus mesenchyme, expanded mouse and human PESCs generate ectopic prostatic tubules, demonstrating their stem cell activity in vivo. This novel method will facilitate the molecular, genomic, and functional characterization of normal and pathologic prostate glands of mouse and human origin. PMID:25702639

Notochord-derived Shh concentrates in close association with the apically positioned basal body in neural target cells and forms a dynamic gradient during neural patterning.

PubMed

Chamberlain, Chester E; Jeong, Juhee; Guo, Chaoshe; Allen, Benjamin L; McMahon, Andrew P

2008-03-01

Sonic hedgehog (Shh) ligand secreted by the notochord induces distinct ventral cell identities in the adjacent neural tube by a concentration-dependent mechanism. To study this process, we genetically engineered mice that produce bioactive, fluorescently labeled Shh from the endogenous locus. We show that Shh ligand concentrates in close association with the apically positioned basal body of neural target cells, forming a dynamic, punctate gradient in the ventral neural tube. Both ligand lipidation and target field response influence the gradient profile, but not the ability of Shh to concentrate around the basal body. Further, subcellular analysis suggests that Shh from the notochord might traffic into the neural target field by means of an apical-to-basal-oriented microtubule scaffold. This study, in which we directly observe, measure, localize and modify notochord-derived Shh ligand in the context of neural patterning, provides several new insights into mechanisms of Shh morphogen action.

Manifestations, Treatment Implications and Speech-Language Consideration in Gorlin Syndrome: A Case Study.

ERIC Educational Resources Information Center

Andrews, Alice E.; Stonestreet, Ruth H.

This paper presents a case study of Gorlin Syndrome, also known as Basal Cell Nevus Syndrome, a rare genetic disorder characterized by widespread developmental defects. Criteria for diagnosis are listed, noting the presence of frequent basal cell carcinomas at a relatively young age and multiple cysts of the jaw. Speech and/or language impairments…

Testing ecological and universal models of body shape and child health using a global sample of infants and young children.

PubMed

Hadley, Craig; Hruschka, Daniel J

2017-11-01

To test whether a risk of child illness is best predicted by deviations from a population-specific growth distribution or a universal growth distribution. Child weight for height and child illness data from 433 776 children (1-59 months) from 47 different low and lower income countries are used in regression models to estimate for each country the child basal weight for height. This study assesses the extent to which individuals within populations deviate from their basal slenderness. It uses correlation and regression techniques to estimate the relationship between child illness (diarrhoea, fever or cough) and basal weight for height, and residual weight for height. In bivariate tests, basal weight for height z-score did not predict the country level prevalence of child illness (r 2  = -0.01, n = 47, p = 0.53), but excess weight for height did (r 2  = 0.14, p < 0.01). At the individual level, household wealth is negatively associated with the odds that a child is reported as ill (beta = -0.04, p < 0.001, n = 433 776) and basal weight for height was not (beta = 0.20, p = 0.27). Deviations from country-specific basal weight for height were negatively associated with the likelihood of illness (beta = -0.13, p < 0.01), indicating a 13% reduction in illness risk for every 0.1 standard deviation increase in residual weight-for-height Conclusion: These results are consistent with the idea that populations may differ in their body slenderness, and that deviations from this body form may predict the risk of childhood illness.

Polarized Ends of Human Macula Densa Cells: Ultrastructural Investigation and Morphofunctional Correlations.

PubMed

Cangiotti, Angela Maria; Lorenzi, Teresa; Zingaretti, Maria Cristina; Fabri, Mara; Morroni, Manrico

2018-05-01

The morphology of the kidney macula densa (MD) has extensively been investigated in animals, whereas human studies are scanty. We studied the fine structure of human MD cells focusing on their apical and basal ends and correlating structure and function. The MD region was examined by transmission electron microscopy in six renal biopsies from patients with kidney disease. Ultrastructural analysis of MD cells was performed on serial sections. MD cells show two polarized ends. The apical portion is characterized by a single, immotile cilium associated with microvilli; apically, cells are joined by adhering junctions. In the basal portion, the cytoplasm contains small, dense granules and numerous, irregular cytoplasmic projections extending to the adjacent extraglomerular mesangium. The projections often contain small, dense granules. A reticulated basement membrane around MD cells separates them from the extraglomerular mesangium. Although the fact that tissue specimens came from patients with kidney disease mandates extreme caution, ultrastructural examination confirmed that MD cells have sensory features due to the presence of the primary cilium, that they are connected by apical adhering junctions forming a barrier that separates the tubular flow from the interstitium, and that they present numerous basal interdigitations surrounded by a reticulated basement membrane. Conceivably, the latter two features are related to the functional activity of the MD. The small, dense granules in the basal cytoplasm and in cytoplasmic projections are likely related to the paracrine function of MD cells. Anat Rec, 301:922-931, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Knockdown of CAVEOLIN-1 Sensitizes Human Basal-Like Triple-Negative Breast Cancer Cells to Radiation.

PubMed

Zou, Man; Li, Yanhui; Xia, Shu; Chu, Qian; Xiao, Xiaoguang; Qiu, Hong; Chen, Yu; Zheng, Zu'an; Liu, Fei; Zhuang, Liang; Yu, Shiying

2017-01-01

Triple-negative breast cancer (TNBC) is a high-risk breast cancer phenotype without specific targeted therapy options and is significantly associated with increased local recurrence in patients treated with radiotherapy. CAVEOLIN-1 (CAV-1)-mediated epidermal growth factor receptor (EGFR) nuclear translocation following irradiation promotes DNA repair and thus induces radiation resistance. In this study, we aimed to determine whether knockdown of CAV-1 enhances the radiosensitivity of basal-like TNBC cell lines and to explore the possible mechanisms. Western blotting was used to compare protein expression in a panel of breast cancer cell lines. Nuclear accumulation of EGFR as well as DNA repair and damage at multiple time points following irradiation with or without CAV-1 siRNA pretreatment were investigated using western blotting and confocal microscopy. The radiosensitizing effect of CAV-1 siRNA was evaluated using a clonogenic assay. Flowcytometry was performed to analyse cell apoptosis and cell cycle alteration. We found that CAV-1 is over-expressed in basal-like TNBC cell lines and barely expressed in HER-2-positive cells; additionally, we observed that HER-2-positive cell lines are more sensitive to irradiation than basal-like TNBC cells. Our findings revealed that radiation-induced EGFR nuclear translocation was impaired by knockdown of CAV-1. In parallel, radiation-induced elevation of DNA repair proteins was also hampered by pretreatment with CAV-1 siRNA before irradiation. Silencing of CAV-1 also promoted DNA damage 24 h after irradiation. Colony formation assays verified that cells could be radiosensitized after knockdown of CAV-1. Furthermore, G2/M cell cycle arrest and apoptosis enhancement may also contribute to the radiosensitizing effect of CAV-1 siRNA. Our results support the hypothesis that CAV-1 knockdown by siRNA causes increased radiosensitivity in basal-like TNBC cells. The mechanisms associated with this effect are reduced DNA repair through delayed CAV-1-associated EGFR nuclear accumulation and induction of G2/M arrest and apoptosis through the combined effects of CAV-1 siRNA and radiation. © 2017 The Author(s). Published by S. Karger AG, Basel.

Ciliated cells of pseudostratified airway epithelium do not become mucous cells after ovalbumin challenge.

PubMed

Pardo-Saganta, Ana; Law, Brandon M; Gonzalez-Celeiro, Meryem; Vinarsky, Vladimir; Rajagopal, Jayaraj

2013-03-01

Mucous cell metaplasia is a hallmark of airway diseases, such as asthma and chronic obstructive pulmonary disease. The majority of human airway epithelium is pseudostratified, but the cell of origin of mucous cells has not been definitively established in this type of airway epithelium. There is evidence that ciliated, club cell (Clara), and basal cells can all give rise to mucus-producing cells in different contexts. Because pseudostratified airway epithelium contains distinct progenitor cells from simple columnar airway epithelium, the lineage relationships of progenitor cells to mucous cells may be different in these two epithelial types. We therefore performed lineage tracing of the ciliated cells of the murine basal cell-containing airway epithelium in conjunction with the ovalbumin (OVA)-induced murine model of allergic lung disease. We genetically labeled ciliated cells with enhanced Yellow Fluorescent Protein (eYFP) before the allergen challenge, and followed the fate of these cells to determine whether they gave rise to newly formed mucous cells. Although ciliated cells increased in number after the OVA challenge, the newly formed mucous cells were not labeled with the eYFP lineage tag. Even small numbers of labeled mucous cells could not be detected, implying that ciliated cells make virtually no contribution to the new goblet cell pool. This demonstrates that, after OVA challenge, new mucous cells do not originate from ciliated cells in a pseudostratified basal cell-containing airway epithelium.

The Structure of the Statocyst of the Freshwater Snail Biomphalaria Glabrata (Pulmonata, Basommatophora)

NASA Technical Reports Server (NTRS)

Gao, Wenyuan; Wiederhold, Michael L.

1997-01-01

The structure of the statocyst of the freshwater snail Biomphalaria glabrata has been examined by light and electron microscopy. The two statocysts are located on the dorsal-lateral side of the left and right pedal ganglion. The statocysts are spherical, fluid-filled capsules with a diameter of approximately 60 microns for young and 110 microns for adult snails. The wall of the cyst is composed of large receptor cells and many smaller supporting cells. The receptor cells bear cilia which are evenly distributed on the apical surface. The cilia have the typical 9+2 internal tubule configuration. Striate rootlets originate from the base of the basal body and run downward into the cytoplasm. Side-roots arise from one side of the basal body and a basal foot from the other. For each receptor cell, the basal foot always points to the periphery of the surface, indicating that the receptor cell is non-polarized. The receptor cells contain cytoplasmic organelles such as mitochondria, ribosomes, rough and smooth endoplasmic reticulum, compact Golgi bodies and multivesicular bodies. Supporting cells bearing microvilli are interposed between the receptor cells. The junction complex between the supporting cells and the receptor cells is composed of adherens and septate junctions, while between supporting cells only the adherens junctions are present. The static nerve arises from the lateral side of the cyst and contains axons in which parallel neurotubules and mitochondria are found. The axons arise directly from the base of the receptor cells without synapse. In the cyst lumen there are unattached statoconia. The statoconia have a plate-like or concentric membranous ring structure. Based on the morphology, the function of the statocyst in Biomphalaria is discussed.

Prkci is required for a non-autonomous signal that coordinates cell polarity during cavitation.

PubMed

Mah, In Kyoung; Soloff, Rachel; Izuhara, Audrey K; Lakeland, Daniel L; Wang, Charles; Mariani, Francesca V

2016-08-01

Polarized epithelia define boundaries, spaces, and cavities within organisms. Cavitation, a process by which multicellular hollow balls or tubes are produced, is typically associated with the formation of organized epithelia. In order for these epithelial layers to form, cells must ultimately establish a distinct apical-basal polarity. Atypical PKCs have been proposed to be required for apical-basal polarity in diverse species. Here we show that while cells null for the Prkci isozyme exhibit some polarity characteristics, they fail to properly segregate apical-basal proteins, form a coordinated ectodermal epithelium, or participate in normal cavitation. A failure to cavitate could be due to an overgrowth of interior cells or to an inability of interior cells to die. Null cells however, do not have a marked change in proliferation rate and are still capable of undergoing cell death, suggesting that alterations in these processes are not the predominant cause of the failed cavitation. Overexpression of BMP4 or EZRIN can partially rescue the phenotype possibly by promoting cell death, polarity, and differentiation. However, neither is sufficient to provide the required cues to generate a polarized epithelium and fully rescue cavitation. Interestingly, when wildtype and Prkci(-/-) ES cells are mixed together, a polarized ectodermal epithelium forms and cavitation is rescued, likely due to the ability of wildtype cells to produce non-autonomous polarity cues. We conclude that Prkci is not required for cells to respond to these cues, though it is required to produce them. Together these findings indicate that environmental cues can facilitate the formation of polarized epithelia and that cavitation requires the proper coordination of multiple basic cellular processes including proliferation, differentiation, cell death, and apical-basal polarization. Copyright © 2016 Elsevier Inc. All rights reserved.

[Morphological changes on cochlear hair cells of rats in simulated weightlessness and inboard noise].

PubMed

2017-06-18

To observe the morphological changes on cochlear hair cells of rats in simulated weightlessness and inboard noise and to investigate the different changes in three turns of hair cells. Thirty-two healthy SD rats, all males, were randomly divided into four groups: control group, weightlessness group, noise group and weightlessness+noise groups (n=8). Then rats were exposed to -30° head down tilt as simulated weightlessness and inboard noise including steady-state noise which was (72±2) dB SPL and impulse noise up to 160 dB SPL in spaceship environment. The control group was kept in normal condition for 8 weeks. Bilateral auditory brainstem response (ABR) thresholds were tested before and after exposure respectively, and immunofluorescence staining and scanning electron microscopy (SEMs) of basilar membrane were applied after exposure. ABR threshold shifts of each group were higher after exposure. There was difference between ABRs of the experiment groups before and after exposure (P<0.05). IF showed that the inner hair cells (IHCs) missing was the main damage in the basal turn of weightlessness group, the hair cells in the middle turn were swell and in the top turn, the hair cells were not clear. In noise group, the main loss happened in the outer hair cells (OHCs) of the outermost layer. In weightlessness+noise group, the nuclear missing in the basal turn was apparent, and mainly happened at the outermost layer. Meanwhile, the missing of hair cells in the middle turn and top turn was seen at the innermost layer. SEM showed that the cilia in the basal turn of weightlessness group were serious lodging, and occasional absence. Furthermore, the basal cilia in noise group became lodged and absent, and the other two turns were seriously missing. And in weightlessness+noise group, the cilia missing in the basal turn was apparently seen. The damage degree of the four groups: weightlessness+noise group>noise group>weightlessness group>control group and the damage degree of the four turns of hair cells: basal turn>mid turn>top turn. The rats exposed to the above environment for 2 weeks displayed obvious changes in cochlea morphology, and the weightlessness +noise group had the most obvious damage.

Basal expression of insulin-like growth factor 1 receptor determines intrinsic resistance of cancer cells to a phosphatidylinositol 3-kinase inhibitor ZSTK474

PubMed Central

Isoyama, Sho; Kajiwara, Gensei; Tamaki, Naomi; Okamura, Mutsumi; Yoshimi, Hisashi; Nakamura, Naoki; Kawamura, Kento; Nishimura, Yumiko; Namatame, Nachi; Yamori, Takao; Dan, Shingo

2015-01-01

Drug resistance often critically limits the efficacy of molecular targeted drugs. Although pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K) is an attractive therapeutic strategy for cancer therapy, molecular determinants for efficacy of PI3K inhibitors (PI3Kis) remain unclear. We previously identified that overexpression of insulin-like growth factor 1 receptor (IGF1R) contributed to the development of drug resistance after long-term exposure to PI3Kis. In this study, we examined the involvement of basal IGF1R expression in intrinsic resistance of drug-naïve cancer cells to PI3Kis and whether inhibition of IGF1R overcomes the resistance. We found that cancer cells highly expressing IGF1R showed resistance to dephosphorylation of Akt and subsequent antitumor effect by ZSTK474 treatment. Knockdown of IGF1R by siRNAs facilitated the dephosphorylation and enhanced the drug efficacy. These cells expressed tyrosine-phosphorylated insulin receptor substrate 1 at high levels, which was dependent on basal IGF1R expression. In these cells, the efficacy of ZSTK474 in vitro and in vivo was improved by its combination with the IGF1R inhibitor OSI-906. Finally, we found a significant correlation between the basal expression level of IGF1R and the inefficacy of ZSTK474 in an in vivo human cancer panel, as well as in vitro. These results suggest that basal IGF1R expression affects intrinsic resistance of cancer cells to ZSTK474, and IGF1R is a promising target to improve the therapeutic efficacy. The current results provide evidence of combination therapy of PI3Kis with IGF1R inhibitors for treating IGF1R-positive human cancers. PMID:25483727

Protective Effects of Trehalose on the Corneal Epithelial Cells

PubMed Central

Aragona, Pasquale; Colosi, Pietro; Colosi, Francesca; Pisani, Antonina; Puzzolo, Domenico; Micali, Antonio

2014-01-01

Purpose. Aim of the present work was to evaluate the effects of the trehalose on the corneal epithelium undergoing alcohol delamination. Methods. Twelve patients undergoing laser subepithelial keratomileusis (LASEK) were consecutively included in the study. The right eyes were pretreated with 3% trehalose eye drops, whilst left eyes were used as control. Epithelial specimens were processed for cells vitality assessment, apoptosis, and light and transmission electron microscopy; a morphometric analysis was performed in both groups. Results. In both trehalose-untreated eyes (TUE) and trehalose-treated eyes (TTE), the percentage of vital cells was similar and no apoptotic cells were observed. In TUE, the corneal epithelium showed superficial cells with reduced microfolds, wing cells with vesicles and dilated intercellular spaces, and dark basal cells with vesicles and wide clefts. In TTE, superficial and wing cells were better preserved, and basal cells were generally clear with intracytoplasmatic vesicles. The morphometric analysis showed statistically significant differences between the two groups: the TTE epithelial height was higher, the basal cells showed larger area and clearer cytoplasm. The distribution of desmosomes and hemidesmosomes was significantly different between the groups. Conclusions. Trehalose administration better preserved morphological and morphometric features of alcohol-treated corneal epithelium, when compared to controls. PMID:25045743

Protective effects of trehalose on the corneal epithelial cells.

PubMed

Aragona, Pasquale; Colosi, Pietro; Rania, Laura; Colosi, Francesca; Pisani, Antonina; Puzzolo, Domenico; Micali, Antonio

2014-01-01

Aim of the present work was to evaluate the effects of the trehalose on the corneal epithelium undergoing alcohol delamination. Twelve patients undergoing laser subepithelial keratomileusis (LASEK) were consecutively included in the study. The right eyes were pretreated with 3% trehalose eye drops, whilst left eyes were used as control. Epithelial specimens were processed for cells vitality assessment, apoptosis, and light and transmission electron microscopy; a morphometric analysis was performed in both groups. In both trehalose-untreated eyes (TUE) and trehalose-treated eyes (TTE), the percentage of vital cells was similar and no apoptotic cells were observed. In TUE, the corneal epithelium showed superficial cells with reduced microfolds, wing cells with vesicles and dilated intercellular spaces, and dark basal cells with vesicles and wide clefts. In TTE, superficial and wing cells were better preserved, and basal cells were generally clear with intracytoplasmatic vesicles. The morphometric analysis showed statistically significant differences between the two groups: the TTE epithelial height was higher, the basal cells showed larger area and clearer cytoplasm. The distribution of desmosomes and hemidesmosomes was significantly different between the groups. Trehalose administration better preserved morphological and morphometric features of alcohol-treated corneal epithelium, when compared to controls.

Conditionally reprogrammed normal and primary tumor prostate epithelial cells: a novel patient-derived cell model for studies of human prostate cancer

PubMed Central

Timofeeva, Olga A.; Palechor-Ceron, Nancy; Li, Guanglei; Yuan, Hang; Krawczyk, Ewa; Zhong, Xiaogang; Liu, Geng; Upadhyay, Geeta; Dakic, Aleksandra; Yu, Songtao; Fang, Shuang; Choudhury, Sujata; Zhang, Xueping; Ju, Andrew; Lee, Myeong-Seon; Dan, Han C.; Ji, Youngmi; Hou, Yong; Zheng, Yun-Ling; Albanese, Chris; Rhim, Johng; Schlegel, Richard; Dritschilo, Anatoly; Liu, Xuefeng

2017-01-01

Our previous study demonstrated that conditional reprogramming (CR) allows the establishment of patient-derived normal and tumor epithelial cell cultures from a variety of tissue types including breast, lung, colon and prostate. Using CR, we have established matched normal and tumor cultures, GUMC-29 and GUMC-30 respectively, from a patient's prostatectomy specimen. These CR cells proliferate indefinitely in vitro and retain stable karyotypes. Most importantly, only tumor-derived CR cells (GUMC-30) produced tumors in xenografted SCID mice, demonstrating maintenance of the critical tumor phenotype. Characterization of cells with DNA fingerprinting demonstrated identical patterns in normal and tumor CR cells as well as in xenografted tumors. By flow cytometry, both normal and tumor CR cells expressed basal, luminal, and stem cell markers, with the majority of the normal and tumor CR cells expressing prostate basal cell markers, CD44 and Trop2, as well as luminal marker, CD13, suggesting a transit-amplifying phenotype. Consistent with this phenotype, real time RT-PCR analyses demonstrated that CR cells predominantly expressed high levels of basal cell markers (KRT5, KRT14 and p63), and low levels of luminal markers. When the CR tumor cells were injected into SCID mice, the expression of luminal markers (AR, NKX3.1) increased significantly, while basal cell markers dramatically decreased. These data suggest that CR cells maintain high levels of proliferation and low levels of differentiation in the presence of feeder cells and ROCK inhibitor, but undergo differentiation once injected into SCID mice. Genomic analyses, including SNP and INDEL, identified genes mutated in tumor cells, including components of apoptosis, cell attachment, and hypoxia pathways. The use of matched patient-derived cells provides a unique in vitro model for studies of early prostate cancer. PMID:28009986

Basal exon skipping and genetic pleiotropy: A predictive model of disease pathogenesis.

PubMed

Drivas, Theodore G; Wojno, Adam P; Tucker, Budd A; Stone, Edwin M; Bennett, Jean

2015-06-10

Genetic pleiotropy, the phenomenon by which mutations in the same gene result in markedly different disease phenotypes, has proven difficult to explain with traditional models of disease pathogenesis. We have developed a model of pleiotropic disease that explains, through the process of basal exon skipping, how different mutations in the same gene can differentially affect protein production, with the total amount of protein produced correlating with disease severity. Mutations in the centrosomal protein of 290 kDa (CEP290) gene are associated with a spectrum of phenotypically distinct human diseases (the ciliopathies). Molecular biologic examination of CEP290 transcript and protein expression in cells from patients carrying CEP290 mutations, measured by quantitative polymerase chain reaction and Western blotting, correlated with disease severity and corroborated our model. We show that basal exon skipping may be the mechanism underlying the disease pleiotropy caused by CEP290 mutations. Applying our model to a different disease gene, CC2D2A (coiled-coil and C2 domains-containing protein 2A), we found that the same correlations held true. Our model explains the phenotypic diversity of two different inherited ciliopathies and may establish a new model for the pathogenesis of other pleiotropic human diseases. Copyright © 2015, American Association for the Advancement of Science.

Gorlin syndrome (nevoid basal cell carcinoma syndrome): update and literature review.

PubMed

Fujii, Katsunori; Miyashita, Toshiyuki

2014-10-01

Gorlin syndrome, also called nevoid basal cell carcinoma syndrome, is an autosomal dominant neurocutaneous disease characterized by developmental anomalies such as palmar pits and rib anomaly, and tumorigenesis such as medulloblastoma and basal cell carcinoma. This syndrome is mainly caused by a mutation of PTCH1, a human homologue of Drosophila patched, including frameshift, missense, or nonsense mutations. Genotype-phenotype correlation has not been established. PTCH1 is a member of hedgehog signaling, which is a highly conserved pathway in vertebrates, composed of hedgehog, SMO, and GLI proteins as well as PTCH1. Given that hedgehog signaling regulates cell growth and development, disorder of this pathway gives rise to not only developmental anomalies but also diverse tumors such as those seen in Gorlin syndrome. We recently reported, for the first time, a nationwide survey of Gorlin syndrome in Japan, noting that the frequency was 1/235,800 in the Japanese population, and that the frequency of basal cell carcinomas was significantly lower in Japan than in the USA and Europe, suggesting that ethnicity and genetic background contribute to these differences. Given that many clinical trials using newly discovered molecular inhibitors are still ongoing, these agents should become the new therapeutic options for hedgehog pathway-dependent tumors in patients with or without Gorlin syndrome. © 2014 Japan Pediatric Society.

Histamine and thrombin modulate endothelial focal adhesion through centripetal and centrifugal forces.

PubMed Central

Moy, A B; Van Engelenhoven, J; Bodmer, J; Kamath, J; Keese, C; Giaever, I; Shasby, S; Shasby, D M

1996-01-01

We examined the contribution of actin-myosin contraction to the modulation of human umbilical vein endothelial cell focal adhesion caused by histamine and thrombin. Focal adhesion was measured as the electrical resistance across a cultured monolayer grown on a microelectrode. Actin-myosin contraction was measured as isometric tension of cultured monolayers grown on a collagen gel. Histamine immediately decreased electrical resistance but returned to basal levels within 3-5 min. Histamine did not increase isometric tension. Thrombin also immediately decreased electrical resistance, but, however, resistance did not return to basal levels for 40-60 min. Thrombin also increased isometric tension, ML-7, an inhibitor of myosin light chain kinase, prevented increases in myosin light chain phosphorylation and increases in tension development in cells exposed to thrombin. ML-7 did not prevent a decline in electrical resistance in cells exposed to thrombin. Instead, ML-7 restored the electrical resistance to basal levels in a shorter period of time (20 min) than cells exposed to thrombin alone. Also, histamine subsequently increased electrical resistance to above basal levels, and thrombin initiated an increase in resistance during the time of peak tension development. Hence, histamine and thrombin modulate endothelial cell focal adhesion through centripetal and centrifugal forces. PMID:8613524

Bayesian prediction of future ice sheet volume using local approximation Markov chain Monte Carlo methods

NASA Astrophysics Data System (ADS)

Davis, A. D.; Heimbach, P.; Marzouk, Y.

2017-12-01

We develop a Bayesian inverse modeling framework for predicting future ice sheet volume with associated formal uncertainty estimates. Marine ice sheets are drained by fast-flowing ice streams, which we simulate using a flowline model. Flowline models depend on geometric parameters (e.g., basal topography), parameterized physical processes (e.g., calving laws and basal sliding), and climate parameters (e.g., surface mass balance), most of which are unknown or uncertain. Given observations of ice surface velocity and thickness, we define a Bayesian posterior distribution over static parameters, such as basal topography. We also define a parameterized distribution over variable parameters, such as future surface mass balance, which we assume are not informed by the data. Hyperparameters are used to represent climate change scenarios, and sampling their distributions mimics internal variation. For example, a warming climate corresponds to increasing mean surface mass balance but an individual sample may have periods of increasing or decreasing surface mass balance. We characterize the predictive distribution of ice volume by evaluating the flowline model given samples from the posterior distribution and the distribution over variable parameters. Finally, we determine the effect of climate change on future ice sheet volume by investigating how changing the hyperparameters affects the predictive distribution. We use state-of-the-art Bayesian computation to address computational feasibility. Characterizing the posterior distribution (using Markov chain Monte Carlo), sampling the full range of variable parameters and evaluating the predictive model is prohibitively expensive. Furthermore, the required resolution of the inferred basal topography may be very high, which is often challenging for sampling methods. Instead, we leverage regularity in the predictive distribution to build a computationally cheaper surrogate over the low dimensional quantity of interest (future ice sheet volume). Continual surrogate refinement guarantees asymptotic sampling from the predictive distribution. Directly characterizing the predictive distribution in this way allows us to assess the ice sheet's sensitivity to climate variability and change.

Multiscale Modeling of Primary Cilium Deformations Under Local Forces and Shear Flows

NASA Astrophysics Data System (ADS)

Peng, Zhangli; Feng, Zhe; Resnick, Andrew; Young, Yuan-Nan

2017-11-01

We study the detailed deformations of a primary cilium under local forces and shear flows by developing a multiscale model based on the state-of-the-art understanding of its molecular structure. Most eukaryotic cells are ciliated with primary cilia. Primary cilia play important roles in chemosensation, thermosensation, and mechanosensation, but the detailed mechanism for mechanosensation is not well understood. We apply the dissipative particle dynamics (DPD) to model an entire well with a primary cilium and consider its different components, including the basal body, microtubule doublets, actin cortex, and lipid bilayer. We calibrate the mechanical properties of individual components and their interactions from experimental measurements and molecular dynamics simulations. We validate the simulations by comparing the deformation profile of the cilium and the rotation of the basal body with optical trapping experiments. After validations, we investigate the deformation of the primary cilium under shear flows. Furthermore, we calculate the membrane tensions and cytoskeleton stresses, and use them to predict the activation of mechanosensitive channels.

The efficacy of facial skin cancer treatment with high-energy pulsed neodymium and Nd:YAG lasers.

PubMed

Moskalik, Konstantin; Kozlov, Alexander; Demin, Eugeny; Boiko, Ernest

2009-04-01

The aim of this study was to assess the curative and cosmetic efficacy of treatment for facial skin cancer using neodymium laser irradiation. Due to the complex anatomy of the area, therapy for facial skin cancer is difficult. Laser irradiation was used for the treatment of 3461 patients with 3624 facial skin cancer lesions of stages T(1-2)N(0)M(0:) 3346 basal cell skin cancers, 188 limited basal cell skin cancer recurrences, and 90 squamous cell skin cancers. Pulsed neodymium (Nd) and Nd:YAG lasers were used as the energy sources. The patients were followed-up from 3 mo to 5 y or more. Patients with basal cell skin cancer treated by irradiation with the Nd laser developed recurrences in 1.8% of cases, and patients treated with the Nd:YAG laser had a recurrence rate of 2.5%. Recurrences following treatment for basal cell skin cancer, and those of squamous cell skin cancer, after irradiation with the Nd laser appeared in 3.7% and 4.4% of patients, respectively. Overall, the frequency of facial skin cancer recurrences after treatment with laser irradiation was 2.1% of all the irradiated tumors. Neodymium laser irradiation is an effective method to treat facial skin cancer of stages T(1-2)N(0)M(0), and results in acceptable cosmetic results.

'En face' ex vivo reflectance confocal microscopy to help the surgery of basal cell carcinoma of the eyelid.

PubMed

Espinasse, Marine; Cinotti, Elisa; Grivet, Damien; Labeille, Bruno; Prade, Virginie; Douchet, Catherine; Cambazard, Frédéric; Thuret, Gilles; Gain, Philippe; Perrot, Jean Luc

2017-07-01

Ex vivo confocal microscopy is a recent imaging technique for the perioperative control of skin tumour margins. Up to date, it has been used in the fluorescence mode and with vertical sections of the specimen margins. The aim of this study was to evaluate its use in the reflectance mode and with a horizontal ('en face') scanning of the surgical specimen in a series of basal cell carcinoma of the eyelid. Prospective consecutive cohort study was performed at the University Hospital of Saint-Etienne, France. Forty-one patients with 42 basal cell carcinoma of the eyelid participated in this study. Basal cell carcinomas were excised with a 2-mm-wide clinically safe margin. The surgical specimens were analysed under ex vivo confocal microscopy in the reflectance mode and with an en face scanning in order to control at a microscopic level if the margins were free from tumour invasion. Histopathogical examination was later performed in order to compare the results. Sensitivity and specificity of ex vivo confocal microscopy for the presence of tumour-free margins. Ex vivo confocal microscopy results were consistent with histopathology in all cases (tumour-free margins in 40 out of 42 samples; sensitivity and specificity of 100%). Ex vivo confocal microscopy in the reflectance mode with an 'en face' scanning can control tumour margins of eyelid basal cell carcinomas and optimize their surgical management. This procedure has the advantage on the fluorescent mode of not needing any contrast agent to examine the samples. © 2016 Royal Australian and New Zealand College of Ophthalmologists.

Cholinergic Inputs from Basal Forebrain Add an Excitatory Bias to Odor Coding in the Olfactory Bulb

PubMed Central

Rothermel, Markus; Carey, Ryan M.; Puche, Adam; Shipley, Michael T.

2014-01-01

Cholinergic modulation of central circuits is associated with active sensation, attention, and learning, yet the neural circuits and temporal dynamics underlying cholinergic effects on sensory processing remain unclear. Understanding the effects of cholinergic modulation on particular circuits is complicated by the widespread projections of cholinergic neurons to telencephalic structures that themselves are highly interconnected. Here we examined how cholinergic projections from basal forebrain to the olfactory bulb (OB) modulate output from the first stage of sensory processing in the mouse olfactory system. By optogenetically activating their axons directly in the OB, we found that cholinergic projections from basal forebrain regulate OB output by increasing the spike output of presumptive mitral/tufted cells. Cholinergic stimulation increased mitral/tufted cell spiking in the absence of inhalation-driven sensory input and further increased spiking responses to inhalation of odorless air and to odorants. This modulation was rapid and transient, was dependent on local cholinergic signaling in the OB, and differed from modulation by optogenetic activation of cholinergic neurons in basal forebrain, which led to a mixture of mitral/tufted cell excitation and suppression. Finally, bulbar cholinergic enhancement of mitral/tufted cell odorant responses was robust and occurred independent of the strength or even polarity of the odorant-evoked response, indicating that cholinergic modulation adds an excitatory bias to mitral/tufted cells as opposed to increasing response gain or sharpening response spectra. These results are consistent with a role for the basal forebrain cholinergic system in dynamically regulating the sensitivity to or salience of odors during active sensing of the olfactory environment. PMID:24672011

Chirality of the cytoskeleton in the origins of cellular asymmetry

PubMed Central

2016-01-01

Self-assembly of two important components of the cytoskeleton of eukaryotic cells, actin microfilaments and microtubules (MTs) results in polar filaments of one chirality. As is true for bacterial flagella, in actin microfilaments, screw direction is important for assembly processes and motility. For MTs, polar orientation within the cell is paramount. The alignment of these elements in the cell cytoplasm gives rise to emergent properties, including the potential for cell differentiation and specialization. Complex MTs with a characteristic chirality are found in basal bodies and centrioles; this chirality is preserved in cilia. In motile cilia, it is reflected in the direction of the effective stroke. The positioning of the basal body or cilia on the cell surface depends on polarity proteins. In evolution, survival depends on global polarity information relayed to the cell in part by orientation of the MT and actin filament cytoskeletons and the chirality of the basal body to determine left and right coordinates within a defined anterior–posterior cell and tissue axis. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’. PMID:27821520

Complexing Methylene Blue with Phosphorus Dendrimers to Increase Photodynamic Activity.

PubMed

Dabrzalska, Monika; Janaszewska, Anna; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

2017-02-23

The efficiency of photodynamic therapy is limited mainly due to low selectivity, unfavorable biodistribution of photosensitizers, and long-lasting skin sensitivity to light. However, drug delivery systems based on nanoparticles may overcome the limitations mentioned above. Among others, dendrimers are particularly attractive as carriers, because of their globular architecture and high loading capacity. The goal of the study was to check whether an anionic phosphorus dendrimer is suitable as a carrier of a photosensitizer-methylene blue (MB). As a biological model, basal cell carcinoma cell lines were used. We checked the influence of the MB complexation on its singlet oxygen production ability using a commercial fluorescence probe. Next, cellular uptake, phototoxicity, reactive oxygen species (ROS) generation, and cell death were investigated. The MB-anionic dendrimer complex (MB-1an) was found to generate less singlet oxygen; however, the complex showed higher cellular uptake and phototoxicity against basal cell carcinoma cell lines, which was accompanied with enhanced ROS production. Owing to the obtained results, we conclude that the photodynamic activity of MB complexed with an anionic dendrimer is higher than free MB against basal cell carcinoma cell lines.

Bad seeds produce bad crops: a single stage-process of prostate tumor invasion

PubMed Central

Man, Yan-gao; Gardner, William A.

2008-01-01

It is a commonly held belief that prostate carcinogenesis is a multi-stage process and that tumor invasion is triggered by the overproduction of proteolytic enzymes. This belief is consistent with data from cell cultures and animal models, whereas is hard to interpret several critical facts, including the presence of cancer in “healthy” young men and cancer DNA phenotype in morphologically normal prostate tissues. These facts argue that alternative pathways may exist for prostate tumor invasion in some cases. Since degradation of the basal cell layer is the most distinct sign of invasion, our recent studies have attempted to identify pre-invasive lesions with focal basal cell layer alterations. Our studies revealed that about 30% of prostate cancer patients harbored normal appearing duct or acinar clusters with a high frequency of focal basal cell layer disruptions. These focally disrupted basal cell layers had significantly reduced cell proliferation and tumor suppressor expression, whereas significantly elevated degeneration, apoptosis, and infiltration of immunoreactive cells. In sharp contrast, associated epithelial cell had significantly elevated proliferation, expression of malignancy-signature markers, and physical continuity with invasive lesions. Based on these and other findings, we have proposed that these normal appearing duct or acinar clusters are derived from monoclonal proliferation of genetically damaged stem cells and could progress directly to invasion through two pathways: 1) clonal in situ transformation (CIST) and 2) multi-potential progenitor mediated “budding” (MPMB). These pathways may contribute to early onset of prostate cancer at young ages, and to clinically more aggressive prostate tumors. PMID:18725981

Mammary collective cell migration involves transient loss of epithelial features and individual cell migration within the epithelium

PubMed Central

Ewald, Andrew J.; Huebner, Robert J.; Palsdottir, Hildur; Lee, Jessie K.; Perez, Melissa J.; Jorgens, Danielle M.; Tauscher, Andrew N.; Cheung, Kevin J.; Werb, Zena; Auer, Manfred

2012-01-01

Normal mammary morphogenesis involves transitions between simple and multilayered epithelial organizations. We used electron microscopy and molecular markers to determine whether intercellular junctions and apico-basal polarity were maintained in the multilayered epithelium. We found that multilayered elongating ducts had polarized apical and basal tissue surfaces both in three-dimensional culture and in vivo. However, individual cells were only polarized on surfaces in contact with the lumen or extracellular matrix. The basolateral marker scribble and the apical marker atypical protein kinase C zeta localized to all interior cell membranes, whereas PAR3 displayed a cytoplasmic localization, suggesting that the apico-basal polarity was incomplete. Despite membrane localization of E-cadherin and β-catenin, we did not observe a defined zonula adherens connecting interior cells. Instead, interior cells were connected through desmosomes and exhibited complex interdigitating membrane protrusions. Single-cell labeling revealed that individual cells were both protrusive and migratory within the epithelial multilayer. Inhibition of Rho kinase (ROCK) further reduced intercellular adhesion on apical and lateral surfaces but did not disrupt basal tissue organization. Following morphogenesis, segregated membrane domains were re-established and junctional complexes re-formed. We observed similar epithelial organization during mammary morphogenesis in organotypic culture and in vivo. We conclude that mammary epithelial morphogenesis involves a reversible, spatially limited, reduction in polarity and intercellular junctions and active individualistic cell migration. Our data suggest that reductions in polarity and adhesion during breast cancer progression might reflect partial recapitulation of a normal developmental program. PMID:22344263

UV-Induced Molecular Signaling Differences in Melanoma and Non-melanoma Skin Cancer.

PubMed

Liu-Smith, Feng; Jia, Jinjing; Zheng, Yan

2017-01-01

There are three major types of skin cancer: melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCC and SCC are often referred to as non-melanoma skin cancer (NMSC). NMSCs are relatively non-lethal and curable by surgery, hence are not reportable in most cancer registries all over the world. Melanoma is the deadliest skin cancer. Its incidence rate (case number) is about 1/10th of that for NMSC, yet its death toll is ~8 fold higher than NMSC.Melanomas arise from melanocytes which are normally located on the basement membrane with dendrites extending into the epidermal keratinocytes. A major known function of melanocytes is to produce pigments which are enclosed by lipid membrane (termed melanosomes) and distribute them into keratinocytes, thus give different shade of skin colors. BCCs arise from basal cells, which are a layer of cells located at the deepest part of epidermis. Basal cells are recently considered to be skin stem cells as they are constantly proliferating and generating keratinocytes which are continuously pushed to the surface and eventually become a dead layer of stratum corneum. Squamous cells are the keratinocytes which resembles fish scale shape, ie, those initiated from basal cells and differentiated into squamous cells. Both basal cells and squamous cells belong to keratinocytes, therefore sometimes BCC and SCC are termed keratinocyte cancer.These three types of cancer share many characteristics, yet they are very different from etiology to progression. One shared characteristic of skin cancer is that, according to the current views, they all are caused by solar or artificial ultraviolet radiation (UVR). UVA and UVB from solar UVR are the major UV bands reaching the earth surface. Both UV types cause DNA damage and immune suppression which play crucial roles in skin carcinogenesis. UVB can be directly absorbed by DNA molecules and thus causes UV-signature DNA damages; UVA, on the other hand, may function through inducing cellular ROS which then causes oxidative DNA damages [1-4]. This chapter will discuss the molecular signaling differences of UVR in melanoma and NMSC.

Clinical Prognosis of Superior Versus Basal Segment Stage I Non-Small Cell Lung Cancer.

PubMed

Handa, Yoshinori; Tsutani, Yasuhiro; Tsubokawa, Norifumi; Misumi, Keizo; Hanaki, Hideaki; Miyata, Yoshihiro; Okada, Morihito

2017-12-01

Despite its extensive size, variations in the clinicopathologic features of tumors in the lower lobe have been little studied. The present study investigated the prognostic differences in tumors originating from the superior and basal segments of the lower lobe in patients with non-small cell lung cancer. Data of 134 patients who underwent lobectomy or segmentectomy with systematic nodal dissection for clinical stage I, radiologically solid-dominant, non-small cell lung cancer in the superior segment (n = 60) or basal segment (n = 74) between April 2007 and December 2015 were retrospectively reviewed. Factors affecting survival were assessed by the Kaplan-Meier method and Cox regression analyses. Prognosis in the superior segment group was worse than that in the basal segment group (5-year overall survival rates 62.6% versus 89.9%, p = 0.0072; and 5-year recurrence-free survival rates 54.4% versus 75.7%, p = 0.032). In multivariable Cox regression analysis, a superior segment tumor was an independent factor for poor overall survival (hazard ratio 3.33, 95% confidence interval: 1.22 to 13.5, p = 0.010) and recurrence-free survival (hazard ratio 2.90, 95% confidence interval: 1.20 to 7.00, p = 0.008). The superior segment group tended to have more pathologic mediastinal lymph node metastases than the basal segment group (15.0% versus 5.4%, p = 0.080). Tumor location was a prognostic factor for clinical stage I non-small cell lung cancer in the lower lobe. Patients with superior segment tumors had worse prognosis than patients with basal segment tumors, with more metastases in mediastinal lymph nodes. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Optogenetic Dissection of the Basal Forebrain Neuromodulatory Control of Cortical Activation, Plasticity, and Cognition

PubMed Central

Brown, Ritchie E.; Hussain Shuler, Marshall G.; Petersen, Carl C.H.; Kepecs, Adam

2015-01-01

The basal forebrain (BF) houses major ascending projections to the entire neocortex that have long been implicated in arousal, learning, and attention. The disruption of the BF has been linked with major neurological disorders, such as coma and Alzheimer's disease, as well as in normal cognitive aging. Although it is best known for its cholinergic neurons, the BF is in fact an anatomically and neurochemically complex structure. Recent studies using transgenic mouse lines to target specific BF cell types have led to a renaissance in the study of the BF and are beginning to yield new insights about cell-type-specific circuit mechanisms during behavior. These approaches enable us to determine the behavioral conditions under which cholinergic and noncholinergic BF neurons are activated and how they control cortical processing to influence behavior. Here we discuss recent advances that have expanded our knowledge about this poorly understood brain region and laid the foundation for future cell-type-specific manipulations to modulate arousal, attention, and cortical plasticity in neurological disorders. SIGNIFICANCE STATEMENT Although the basal forebrain is best known for, and often equated with, acetylcholine-containing neurons that provide most of the cholinergic innervation of the neocortex, it is in fact an anatomically and neurochemically complex structure. Recent studies using transgenic mouse lines to target specific cell types in the basal forebrain have led to a renaissance in this field and are beginning to dissect circuit mechanisms in the basal forebrain during behavior. This review discusses recent advances in the roles of basal forebrain cholinergic and noncholinergic neurons in cognition via their dynamic modulation of cortical activity. PMID:26468190

The Distribution of Basal Water Beneath the Greenland Ice Sheet from Radio-Echo Sounding

NASA Astrophysics Data System (ADS)

Jordan, T.; Williams, C.; Schroeder, D. M.; Martos, Y. M.; Cooper, M.; Siegert, M. J.; Paden, J. D.; Huybrechts, P.; Bamber, J. L.

2017-12-01

There is widespread, but often indirect, evidence that a significant fraction of the Greenland Ice Sheet is thawed at the bed. This includes major outlet glaciers and around the NorthGRIP ice-core in the interior. However, the ice-sheet-wide distribution of basal water is poorly constrained by existing observations, and the spatial relationship between basal water and other ice-sheet and subglacial properties is therefore largely unexplored. In principle, airborne radio-echo sounding (RES) surveys provide the necessary information and spatial coverage to infer the presence of basal water at the ice-sheet scale. However, due to uncertainty and spatial variation in radar signal attenuation, the commonly used water diagnostic, bed-echo reflectivity, is highly ambiguous and prone to spatial bias. Here we introduce a new RES diagnostic for the presence of basal water which incorporates both sharp step-transitions and rapid fluctuations in bed-echo reflectivity. This has the advantage of being (near) independent of attenuation model, and enables a decade of recent Operation Ice Bride RES survey data to be combined in a single map for basal water. The ice-sheet-wide water predictions are compared with: bed topography and drainage network structure, existing knowledge of the thermal state and geothermal heat flux, and ice velocity. In addition to the fast flowing ice-sheet margins, we also demonstrate widespread water routing and storage in parts of the slow-flowing northern interior. Notably, this includes a quasi-linear `corridor' of basal water, extending from NorthGRIP to Petermann glacier, which spatially correlates with a region of locally high (magnetic-derived) geothermal heat flux. The predicted water distribution places a new constraint upon the basal thermal state of the Greenland Ice Sheet, and could be used as an input for ice-sheet model simulations.

Gorlin syndrome.

PubMed

Devi, Basanti; Behera, Binodini; Patro, Sibasish; Pattnaik, Subhransu S; Puhan, Manas R

2013-05-01

Gorlin Syndrome, a rare genodermatosis, otherwise known as Nevoid basal cell carcinoma syndrome (NBCCS) is a multisystem disease affecting skin, nervous system, eyes, endocrine glands, and bones. It is characterized by multiple basal cell carcinomas, palmoplantar pits, jaw cysts, and bony deformities like kyphoscoliosis and frontal bossing. We would like to report a case of Gorlin syndrome with classical features, as this is a rare genodermatosis.

Predicting tree species presence and basal area in Utah: A comparison of stochastic gradient boosting, generalized additive models, and tree-based methods

USGS Publications Warehouse

Moisen, Gretchen G.; Freeman, E.A.; Blackard, J.A.; Frescino, T.S.; Zimmermann, N.E.; Edwards, T.C.

2006-01-01

Many efforts are underway to produce broad-scale forest attribute maps by modelling forest class and structure variables collected in forest inventories as functions of satellite-based and biophysical information. Typically, variants of classification and regression trees implemented in Rulequest's?? See5 and Cubist (for binary and continuous responses, respectively) are the tools of choice in many of these applications. These tools are widely used in large remote sensing applications, but are not easily interpretable, do not have ties with survey estimation methods, and use proprietary unpublished algorithms. Consequently, three alternative modelling techniques were compared for mapping presence and basal area of 13 species located in the mountain ranges of Utah, USA. The modelling techniques compared included the widely used See5/Cubist, generalized additive models (GAMs), and stochastic gradient boosting (SGB). Model performance was evaluated using independent test data sets. Evaluation criteria for mapping species presence included specificity, sensitivity, Kappa, and area under the curve (AUC). Evaluation criteria for the continuous basal area variables included correlation and relative mean squared error. For predicting species presence (setting thresholds to maximize Kappa), SGB had higher values for the majority of the species for specificity and Kappa, while GAMs had higher values for the majority of the species for sensitivity. In evaluating resultant AUC values, GAM and/or SGB models had significantly better results than the See5 models where significant differences could be detected between models. For nine out of 13 species, basal area prediction results for all modelling techniques were poor (correlations less than 0.5 and relative mean squared errors greater than 0.8), but SGB provided the most stable predictions in these instances. SGB and Cubist performed equally well for modelling basal area for three species with moderate prediction success, while all three modelling tools produced comparably good predictions (correlation of 0.68 and relative mean squared error of 0.56) for one species. ?? 2006 Elsevier B.V. All rights reserved.

Acetylcysteine Rinse in Reducing Saliva Thickness and Mucositis in Patients With Head and Neck Cancer Undergoing Radiation Therapy

ClinicalTrials.gov

2018-04-17

Mucositis; Oral Complications; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Adenoid Cystic Carcinoma of the Oral Cavity; Stage I Basal Cell Carcinoma of the Lip; Stage I Lymphoepithelioma of the Nasopharynx; Stage I Lymphoepithelioma of the Oropharynx; Stage I Mucoepidermoid Carcinoma of the Oral Cavity; Stage I Salivary Gland Cancer; Stage I Squamous Cell Carcinoma of the Larynx; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Nasopharynx; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Verrucous Carcinoma of the Larynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Adenoid Cystic Carcinoma of the Oral Cavity; Stage II Basal Cell Carcinoma of the Lip; Stage II Lymphoepithelioma of the Nasopharynx; Stage II Lymphoepithelioma of the Oropharynx; Stage II Mucoepidermoid Carcinoma of the Oral Cavity; Stage II Salivary Gland Cancer; Stage II Squamous Cell Carcinoma of the Larynx; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Larynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage III Basal Cell Carcinoma of the Lip; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Lymphoepithelioma of the Oropharynx; Stage III Mucoepidermoid Carcinoma of the Oral Cavity; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVA Basal Cell Carcinoma of the Lip; Stage IVA Lymphoepithelioma of the Oropharynx; Stage IVA Mucoepidermoid Carcinoma of the Oral Cavity; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVB Basal Cell Carcinoma of the Lip; Stage IVB Lymphoepithelioma of the Oropharynx; Stage IVB Mucoepidermoid Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVC Basal Cell Carcinoma of the Lip; Stage IVC Lymphoepithelioma of the Oropharynx; Stage IVC Mucoepidermoid Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

Brooke-Spiegler syndrome presenting multiple concurrent cutaneous and parotid gland neoplasms: cytologic findings on fine-needle sample and description of a novel mutation of the CYLD gene.

PubMed

Malzone, Maria Gabriella; Campanile, Anna Cipolletta; Losito, Nunzia Simona; Longo, Francesco; Perri, Francesco; Caponigro, Francesco; Schiavone, Concetta; Ionna, Franco; Maiello, Francesco; Martinuzzi, Claudia; Nasti, Sabina; Botti, Gerardo; Fulciniti, Franco

2015-08-01

Multiple dermal cylindromas and membranous basal cell adenoma of parotid gland in a 67-year-old woman with Brooke-Spiegler syndrome (BSS) were examined by fine-needle cytology. Histology, immunochemistry, and CYLD germline mutation testing were also performed. Cytomorphology and immunochemistry of the two lesions showed basaloid neoplasms, remarkably similar, composed by proliferating epithelial cells of basal type accompanied by a smaller proportion of myoepithelial cells. CYLD gene showed a novel germline splice acceptor site mutation (c.2042-1G>C) with skipping of the entire exon 15. The occurrence of analogous tumors, dermal cylindromas, and membranous basal cell adenoma of the parotid gland, in the same patient may result from the action of a single gene on ontogenetically similar stem cells. Therefore, patients with BSS should be offered a genetic counselling for an early and correct diagnosis. © 2015 Wiley Periodicals, Inc.

Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome)

PubMed Central

Kiran, N. K.; Tilak Raj, T. N.; Mukunda, K. S.; Rajashekar Reddy, V.

2012-01-01

The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient. PMID:23633824

Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome).

PubMed

Kiran, N K; Tilak Raj, T N; Mukunda, K S; Rajashekar Reddy, V

2012-10-01

The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient.

Fine genetic mapping of the gene for nevoid basal cell carcinoma syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wicking, C.; Berkman, J.; Wainwright, B.

1994-08-01

Nevoid basal cell carcinoma syndrome (NBCCS, or Gorlin syndrome) is a cancer predisposition syndrome characterized by multiple basal cell carcinomas and diverse developmental defects. The gene responsible for NBCCS, which is most likely to be a tumor suppressor gene, has previously been mapped to 9q22.3-q31 in a 12-cM interval between the microsatellite marker loci D9S12.1 and D9S109. Combined multipoint and haplotype analyses of additional polymorphisms in this region in our collection of Australasian pedigrees have further refined the localization of the gene to between the markers D9S196 and D9S180, an interval reported to be approximately 2 cM. 27 refs., 4more » figs., 1 tab.« less

Differentiation of seborrheic keratosis from basal cell carcinoma, nevi and melanoma by RGB autofluorescence imaging

PubMed Central

Lihachev, Alexey; Lihacova, Ilze; Plorina, Emilija V.; Lange, Marta; Derjabo, Alexander; Spigulis, Janis

2018-01-01

A clinical trial on the autofluorescence imaging of skin lesions comprising 16 dermatologically confirmed pigmented nevi, 15 seborrheic keratosis, 2 dysplastic nevi, histologically confirmed 17 basal cell carcinomas and 1 melanoma was performed. The autofluorescence spatial properties of the skin lesions were acquired by smartphone RGB camera under 405 nm LED excitation. The diagnostic criterion is based on the calculation of the mean autofluorescence intensity of the examined lesion in the spectral range of 515 nm–700 nm. The proposed methodology is able to differentiate seborrheic keratosis from basal cell carcinoma, pigmented nevi and melanoma. The sensitivity and specificity of the proposed method was estimated as being close to 100%. The proposed methodology and potential clinical applications are discussed in this article. PMID:29675324

Differentiation of seborrheic keratosis from basal cell carcinoma, nevi and melanoma by RGB autofluorescence imaging.

PubMed

Lihachev, Alexey; Lihacova, Ilze; Plorina, Emilija V; Lange, Marta; Derjabo, Alexander; Spigulis, Janis

2018-04-01

A clinical trial on the autofluorescence imaging of skin lesions comprising 16 dermatologically confirmed pigmented nevi, 15 seborrheic keratosis, 2 dysplastic nevi, histologically confirmed 17 basal cell carcinomas and 1 melanoma was performed. The autofluorescence spatial properties of the skin lesions were acquired by smartphone RGB camera under 405 nm LED excitation. The diagnostic criterion is based on the calculation of the mean autofluorescence intensity of the examined lesion in the spectral range of 515 nm-700 nm. The proposed methodology is able to differentiate seborrheic keratosis from basal cell carcinoma, pigmented nevi and melanoma. The sensitivity and specificity of the proposed method was estimated as being close to 100%. The proposed methodology and potential clinical applications are discussed in this article.

Basal cell carcinomas of the areola-nipple complex: case reports and review of the literature.

PubMed

Betti, Roberto; Martino, Patrizia; Moneghini, Laura; Vergani, Raffaelle; Tolomio, Elena; Crosti, Carlo

2003-11-01

Two white men 57 and 39 years old, and a 47-year-old white woman were seen with slowly developing papulo-nodular lesions of the areola-nipple complex. None of the patients presented with regional lymphadenopathy, history of trauma, or relevant sun-exposure. After excison of the mass, the histologic diagnosis of basal cell carcinoma was made. At two years of follow-up, no recurrence was evident. The low incidence of basal cell carcinoma in this particular site allows us to consider the areola-nipple complex location as unusual. Moreover, literature reports do not suggest that these BCCs have an increased potential for malignancy. The treatment options depend on the extension of the tumor and on the possible involvement of the areola-nipple complex and mammary tissue.

The role of cardiac vagal tone and inhibitory control in pre-schoolers' listening comprehension.

PubMed

Scrimin, Sara; Patron, Elisabetta; Florit, Elena; Palomba, Daniela; Mason, Lucia

2017-12-01

This study investigated the role of basal cardiac activity and inhibitory control at the beginning of the school year in predicting oral comprehension at the end of the year in pre-schoolers. Forty-three, 4-year-olds participated in the study. At the beginning of the school year children's electrocardiogram at rest was registered followed by the assessment of inhibitory control as well as verbal working memory and verbal ability. At the end of the year all children were administered a listening comprehension ability measure. A stepwise regression showed a significant effect of basal cardiac vagal tone in predicting listening comprehension together with inhibitory control and verbal ability. These results are among the first to show the predictive role of basal cardiac vagal tone and inhibitory control in pre-schoolers' oral text comprehension, and offer new insight into the association between autonomic regulation of the heart, inhibitory control, and cognitive activity at a young age. © 2017 Wiley Periodicals, Inc.

Social context differentially modulates activity of two interneuron populations in an avian basal ganglia nucleus

PubMed Central

2016-01-01

Basal ganglia circuits are critical for the modulation of motor performance across behavioral states. In zebra finches, a cortical-basal ganglia circuit dedicated to singing is necessary for males to adjust their song performance and transition between spontaneous singing, when they are alone (“undirected” song), and a performance state, when they sing to a female (“female-directed” song). However, we know little about the role of different basal ganglia cell types in this behavioral transition or the degree to which behavioral context modulates the activity of different neuron classes. To investigate whether interneurons in the songbird basal ganglia encode information about behavioral state, I recorded from two interneuron types, fast-spiking interneurons (FSI) and external pallidal (GPe) neurons, in the songbird basal ganglia nucleus area X during both female-directed and undirected singing. Both cell types exhibited higher firing rates, more frequent bursting, and greater trial-by-trial variability in firing when male zebra finches produced undirected songs compared with when they produced female-directed songs. However, the magnitude and direction of changes to the firing rate, bursting, and variability of spiking between when birds sat silently and when they sang undirected and female-directed song varied between FSI and GPe neurons. These data indicate that social modulation of activity important for eliciting changes in behavioral state is present in multiple cell types within area X and suggests that social interactions may adjust circuit dynamics during singing at multiple points within the circuit. PMID:27628208

Alterations in neuronal activity in basal ganglia-thalamocortical circuits in the parkinsonian state

PubMed Central

Galvan, Adriana; Devergnas, Annaelle; Wichmann, Thomas

2015-01-01

In patients with Parkinson’s disease and in animal models of this disorder, neurons in the basal ganglia and related regions in thalamus and cortex show changes that can be recorded by using electrophysiologic single-cell recording techniques, including altered firing rates and patterns, pathologic oscillatory activity and increased inter-neuronal synchronization. In addition, changes in synaptic potentials or in the joint spiking activities of populations of neurons can be monitored as alterations in local field potentials (LFPs), electroencephalograms (EEGs) or electrocorticograms (ECoGs). Most of the mentioned electrophysiologic changes are probably related to the degeneration of diencephalic dopaminergic neurons, leading to dopamine loss in the striatum and other basal ganglia nuclei, although degeneration of non-dopaminergic cell groups may also have a role. The altered electrical activity of the basal ganglia and associated nuclei may contribute to some of the motor signs of the disease. We here review the current knowledge of the electrophysiologic changes at the single cell level, the level of local populations of neural elements, and the level of the entire basal ganglia-thalamocortical network in parkinsonism, and discuss the possible use of this information to optimize treatment approaches to Parkinson’s disease, such as deep brain stimulation (DBS) therapy. PMID:25698937

The rhizoplast of chrysomonads, a basal body-nucleus connector that polarises the dividing spindle.

PubMed

Brugerolle, G; Mignot, J-P

2003-09-01

An ultrastructure study of the rhizoplast in Synura petersenii, Mallomonas fastigiata, and M. insignis shows that it consists of 15-20 striated rootlets that form a claw or an incomplete cone over the nucleus. These rootlets course along one face of the nucleus between the nuclear membrane and the cis-face of the Golgi stack of cisternae. They converge and merge above the nucleus, forming a stub attached to the proximal section of the two basal bodies. These cross-striated rootlets are composed of closely packed longitudinal microfibrils. By immunofluorescence, the basal bodies and the rootlets forming the claw were decorated by the anti-centrin monoclonal antibody ICL19 raised against the Paramecium tetraurelia acidic centrin protein and by two antibodies raised against the striated parabasal and costal striated fibres of trichomonads. Only the anti-centrin monoclonal antibody 20H5 raised against Chlamydomonas reinhardtii centrin strongly labelled the 20-22 kDa protein bands from the extracted cytoskeleton of S. petersenii by immunoblotting. Electron micrographs of mitosis in S. petersenii cells revealed that the segregated pairs of basal bodies are linked by the striated rootlets of the rhizoplast to the poles of the mitotic spindle. The spindle microtubules arise perpendicularly from the striated rootlets of the basal body-nucleus connector forming the centrosome. In conclusion, in these cells there is a basal body-nucleus connector similar to that of C. reinhardtii and other chlorophytes. It contains centrin proteins, it is involved in the linkage of the basal bodies to the nucleus and is a component of the spindle pole body or centrosome in the dividing cell.

Macrophages are required for dendritic cell uptake of respiratory syncytial virus from an infected epithelium.

PubMed

Ugonna, Kelechi; Bingle, Colin D; Plant, Karen; Wilson, Kirsty; Everard, Mark L

2014-01-01

We have previously shown that the respiratory syncytial virus [RSV] can productively infect monocyte derived dendritic cells [MoDC] and remain dormant within the same cells for prolonged periods. It is therefore possible that infected dendritic cells act as a reservoir within the airways of individuals between annual epidemics. In the present study we explored the possibility that sub-epithelial DCs can be infected with RSV from differentiated bronchial epithelium and that in turn RSV from DCs can infect the epithelium. A dual co-culture model was established in which a differentiated primary airway epithelium on an Air Liquid Interface (ALI) was cultured on a transwell insert and MoDCs were subsequently added to the basolateral membrane of the insert. Further experiments were undertaken using a triple co-culture model in which in which macrophages were added to the apical surface of the differentiated epithelium. A modified RSV [rr-RSV] expressing a red fluorescent protein marker of replication was used to infect either the MoDCs or the differentiated epithelium and infection of the reciprocal cell type was assessed using confocal microscopy. Our data shows that primary epithelium became infected when rr-RSV infected MoDCs were introduced onto the basal surface of the transwell insert. MoDCs located beneath the epithelium did not become infected with virus from infected epithelial cells in the dual co-culture model. However when macrophages were present on the apical surface of the primary epithelium infection of the basal MoDCs occurred. Our data suggests that RSV infected dendritic cells readily transmit infection to epithelial cells even when they are located beneath the basal layer. However macrophages appear to be necessary for the transmission of infection from epithelial cells to basal dendritic cells.

THE ANATOMIC SITE OF THE TRANSEPITHELIAL PERMEABILITY BARRIERS OF TOAD BLADDER

PubMed Central

DiBona, Donald R.; Civan, Mortimer M.; Leaf, Alexander

1969-01-01

An examination of the mucosal epithelium of the urinary bladder of the toad reveals that the two major cell types which abut on the urinary surface, the granular and mitochondria-rich cells, also contact the basement membrane. Thus, the epithelium functions as a single cell layer. Although basal cells are interpolated between the granular cells and the basement membrane over a large portion of the epithelium, they do not constitute an additional continuous cell layer. This finding is consistent with extensive physiological data which had assumed that the major permeability barriers of this epithelium were the apical and basal-lateral plasma membranes of a single layer of cells. PMID:5782445

Dishevelled links basal body docking and orientation in ciliated epithelial cells

PubMed Central

Vladar, Eszter K.; Axelrod, Jeffrey D.

2014-01-01

Some epithelia contain cells with multiple, motile cilia that beat in a concerted fashion. New tools and experimental systems have facilitated molecular studies of cilium biogenesis and of the coordinated planar polarization of cilia that leads to their concerted motility. Recent, elegant work by Park and colleagues, using embryonic frog epidermis, demonstrates that Dishevelled (Dvl), a key regulator of both the Wnt/β-catenin and Planar Cell Polarity (PCP) pathways, controls both the docking and planar polarization of ciliary basal bodies. PMID:18819800

Combined influence of basal media and fibroblast growth factor on the expansion and differentiation capabilities of adipose-derived stem cells.

PubMed

Ahearne, Mark; Lysaght, Joanne; Lynch, Amy P

2014-01-01

Interest in adipose-derived stem cells (ASCs) has increased in recent years due to their multi-linage differentiation capabilities. While much work has been done to optimize the differentiation media, few studies have focused on examining the influence of different expansion media on cell behavior. In this study, three basal media (low glucose Dulbecco's modified Eagle's medium (DMEM), high glucose DMEM and DMEM-F12) supplemented with or without fibroblast growth factor 2 (FGF) were examined to assess their suitability for expanding ASCs. Flow cytometry, colony-forming unit assays (CFU-Fs) and differentiation assays were utilized to study cell behavior. High glucose media CFU-Fs produced fewest colonies while the addition of FGF increased colony size. By passage 2, the majority of cells were positive for CD44, 45, 73, 90 and 105 and negative for CD14, 31 and 45, indicating a mesenchymal phenotype. A sub-population of CD34 positive cells was present among passage 2 cells; however, by passage 4 the cells were negative for CD34. FGF has a negative effective on passage 4 ASC adipogenesis and high glucose media plus FGF-enhanced osteogenic capacity of passage 4 ASCs. FGF supplemented basal media were most suitable for chondrogenesis. High glucose media plus FGF appeared to be the most beneficial for priming ASCs to induce a keratocyte phenotype. These findings demonstrate the reciprocal effect FGF and basal media have on ASCs. This research has implications for those interested regenerating bone, cartilage, cornea or adipose tissues.

Trophoblast specialisations during pregnancy in the tammar wallaby, Macropus eugenii: a morphological and lectin histochemical study.

PubMed

Jones, C J P; Skepper, J N; Renfree, M B; Aplin, J D

2014-07-01

The tammar wallaby has a short gestation (26.5 days) and vascular modifications to expedite transport during that brief pregnancy. Here we examine trophoblast structural attributes that would facilitate materno-fetal exchange. Four specimens of Macropus eugenii between days 23 and 26 gestation were examined using electron microscopy and 24 lectins to characterise glycosylated secretions and their internalisation. Two trophoblast phenotypes were found, flattened cells generally in contact with the underlying uterine epithelium and giant cells associated with histiotrophe. The latter appeared to penetrate uterine clefts, occasionally detach and become necrotic. Lectin histochemistry and ultrastructure indicated the presence of many lysosomes and residual bodies especially in trophoblast giant cells; these contained glycans, mainly apically, which were also detected in secretions and cell debris. Trophoblast basal membranes bore extensive filopodia. Giant cells were less common in vascular trilaminar areas and here the trophoblast barrier became thinner near term. Loss of Maackia amurensis agglutinin binding suggested cleavage of terminal sialic acid residues as an early post-internalisation event in the trophoblast. Lectin staining indicated degradation occurred in an apical-basal direction, and the heavily glycosylated basal membrane appeared specialised for transport out of the cell. Granules seen ultrastructurally and histochemically, particularly in giant trophoblast cells of the bilaminar area, suggest that internalised histiotrophe is broken down here and nutrients transferred to the embryo via the specialised basal plasma membrane. The trilaminar vascular area contained mostly flattened trophoblast cells, supporting the suggestion that gaseous exchange is its primary function. Copyright © 2014 Elsevier Ltd. All rights reserved.

Towards a biopsychological understanding of costly punishment: the role of basal cortisol.

PubMed

Pfattheicher, Stefan; Keller, Johannes

2014-01-01

Recent findings have documented a negative relation of basal endogenous cortisol and aggression after a provocation (i.e., reactive aggression) in humans. We build on these findings and investigated the relation of endogenous cortisol and reactive aggression in a social dilemma situation, that is, costly punishment of individuals who did not appropriately contribute to a common group project. Specifically, we predicted that basal cortisol is negatively related to costly punishment of uncooperative individuals. In the present study, basal cortisol was assessed prior to a public goods game with the option to punish other group members. In line with previous research on reactive aggression and basal cortisol, we found that basal cortisol was indeed negatively related to costly punishment. The findings are important for understanding costly punishment because this tendency has been documented as a possible basis for the evolution of cooperation.

Towards a Biopsychological Understanding of Costly Punishment: The Role of Basal Cortisol

PubMed Central

Pfattheicher, Stefan; Keller, Johannes

2014-01-01

Recent findings have documented a negative relation of basal endogenous cortisol and aggression after a provocation (i.e., reactive aggression) in humans. We build on these findings and investigated the relation of endogenous cortisol and reactive aggression in a social dilemma situation, that is, costly punishment of individuals who did not appropriately contribute to a common group project. Specifically, we predicted that basal cortisol is negatively related to costly punishment of uncooperative individuals. In the present study, basal cortisol was assessed prior to a public goods game with the option to punish other group members. In line with previous research on reactive aggression and basal cortisol, we found that basal cortisol was indeed negatively related to costly punishment. The findings are important for understanding costly punishment because this tendency has been documented as a possible basis for the evolution of cooperation. PMID:24416441

The Ptch1DL mouse: a new model to study lambdoid craniosynostosis and basal cell nevus syndrome associated skeletal defects

PubMed Central

Feng, Weiguo; Choi, Irene; Clouthier, David E.; Niswander, Lee; Williams, Trevor

2013-01-01

Mouse models provide valuable opportunities for probing the underlying pathology of human birth defects. Employing an ENU-based screen for recessive mutations affecting craniofacial anatomy we isolated a mouse strain, Dogface-like (DL), with abnormal skull and snout morphology. Examination of the skull indicated that these mice developed craniosynostosis of the lambdoid suture. Further analysis revealed skeletal defects related to the pathology of basal cell nevus syndrome (BCNS) including defects in development of the limbs, scapula, ribcage, secondary palate, cranial base, and cranial vault. In humans, BCNS is often associated with mutations in the Hedgehog receptor PTCH1 and genetic mapping in DL identified a point mutation at a splice donor site in Ptch1. Using genetic complementation analysis we determined that DL is a hypomorphic allele of Ptch1, leading to increased Hedgehog signaling. Two aberrant transcripts are generated by the mutated Ptch1DL gene, which would be predicted to reduce significantly the levels of functional Patched1 protein. This new Ptch1 allele broadens the mouse genetic reagents available to study the Hedgehog pathway and provides a valuable means to study the underlying skeletal abnormalities in BCNS. In addition, these results strengthen the connection between elevated Hedgehog signaling and craniosynostosis. PMID:23897749

Synaptotagmin 4 Regulates Pancreatic β Cell Maturation by Modulating the Ca2+ Sensitivity of Insulin Secretion Vesicles.

PubMed

Huang, Chen; Walker, Emily M; Dadi, Prasanna K; Hu, Ruiying; Xu, Yanwen; Zhang, Wenjian; Sanavia, Tiziana; Mun, Jisoo; Liu, Jennifer; Nair, Gopika G; Tan, Hwee Yim Angeline; Wang, Sui; Magnuson, Mark A; Stoeckert, Christian J; Hebrok, Matthias; Gannon, Maureen; Han, Weiping; Stein, Roland; Jacobson, David A; Gu, Guoqiang

2018-05-07

Islet β cells from newborn mammals exhibit high basal insulin secretion and poor glucose-stimulated insulin secretion (GSIS). Here we show that β cells of newborns secrete more insulin than adults in response to similar intracellular Ca 2+ concentrations, suggesting differences in the Ca 2+ sensitivity of insulin secretion. Synaptotagmin 4 (Syt4), a non-Ca 2+ binding paralog of the β cell Ca 2+ sensor Syt7, increased by ∼8-fold during β cell maturation. Syt4 ablation increased basal insulin secretion and compromised GSIS. Precocious Syt4 expression repressed basal insulin secretion but also impaired islet morphogenesis and GSIS. Syt4 was localized on insulin granules and Syt4 levels inversely related to the number of readily releasable vesicles. Thus, transcriptional regulation of Syt4 affects insulin secretion; Syt4 expression is regulated in part by Myt transcription factors, which repress Syt4 transcription. Finally, human SYT4 regulated GSIS in EndoC-βH1 cells, a human β cell line. These findings reveal the role that altered Ca 2+ sensing plays in regulating β cell maturation. Copyright © 2018 Elsevier Inc. All rights reserved.

A Toxoplasma MORN1 Null Mutant Undergoes Repeated Divisions but Is Defective in Basal Assembly, Apicoplast Division and Cytokinesis

PubMed Central

Lorestani, Alexander; Sheiner, Lilach; Yang, Kevin; Robertson, Seth D.; Sahoo, Nivedita; Brooks, Carrie F.; Ferguson, David J. P.; Striepen, Boris; Gubbels, Marc-Jan

2010-01-01

The membrane occupation and recognition nexus protein 1 (MORN1) is highly conserved among apicomplexan parasites and is associated with several structures that have a role in cell division. Here we dissected the role of MORN1 using the relatively simple budding process of Toxoplasma gondii as a model. Ablation of MORN1 in a conditional null mutant resulted in pronounced defects suggesting a central role for MORN1 in apicoplast segregation and in daughter cell budding. Lack of MORN1 resulted in double-headed parasites. These Janus-headed parasites form two complete apical complexes but fail to assemble a basal complex. Moreover, these parasites were capable of undergoing several more budding rounds resulting in the formation of up to 16-headed parasites conjoined at the basal end. Despite this segregation defect, the mother's cytoskeleton was completely disassembled in every budding round. Overall this argues that successful completion of the budding is not required for cell cycle progression. None of the known basal complex components, including a set of recently identified inner membrane complex (IMC) proteins, localized correctly in these multi-headed parasites. These data suggest that MORN1 is essential for assembly of the basal complex, and that lack of the basal complex abolishes the contractile capacity assigned to the basal complex late in daughter formation. Consistent with this hypothesis we observe that MORN1 mutants fail to efficiently constrict and divide the apicoplast. We used the null background provided by the mutant to dissect the function of subdomains of the MORN1 protein. This demonstrated that deletion of a single MORN domain already prevented the function of MORN1 whereas a critical role for the short linker between MORN domains 6 and 7 was identified. In conclusion, MORN1 is required for basal complex assembly and loss of MORN1 results in defects in apicoplast division and daughter segregation. PMID:20808817

Metastatic basal cell carcinoma: case series and review of the literature.

PubMed

Tang, Simon; Thompson, Stephen; Smee, Robert

2017-05-01

Metastatic basal cell carcinoma is exceedingly uncommon, with a poorly defined natural history, and its incidence, risk factors, patterns of spread, prognosis and potential treatment options are not well understood. This retrospective single institution case series aims to shed light on these issues. Aggressive local management in patients with locoregional disease may result in long-term survivors. © 2016 The Australasian College of Dermatologists.

A multispectral imaging approach for diagnostics of skin pathologies

NASA Astrophysics Data System (ADS)

Lihacova, Ilze; Derjabo, Aleksandrs; Spigulis, Janis

2013-06-01

Noninvasive multispectral imaging method was applied for different skin pathology such as nevus, basal cell carcinoma, and melanoma diagnostics. Developed melanoma diagnostic parameter, using three spectral bands (540 nm, 650 nm and 950 nm), was calculated for nevus, melanoma and basal cell carcinoma. Simple multispectral diagnostic device was established and applied for skin assessment. Development and application of multispectral diagnostics method described further in this article.

Natural killer cells and HLA-G expression in the basal decidua of human placenta adhesiva.

PubMed

van Beekhuizen, H J; Joosten, I; Lotgering, F K; Bulten, J; van Kempen, L C

2010-12-01

Retained placenta is caused by abnormal adherence of the placenta to the uterine wall, leading to delayed expulsion of the placenta and causing postpartum haemorrhage. The mildest form of retained placenta is the placenta adhesiva (PA), of which the cause is unknown. The aim of our study was to explore possible differences in immune response in the basal decidua between PA and control placentas (CP). We performed a descriptive analysis of immunohistochemical differences in 17 PA and 10 CP. Our results show that in PA the amount of uterine natural killer (uNK) cells is significantly reduced (0.2 uNK cell/standardised area) as compared to CP (9.8 uNK cell/standardised area, p < 0.001) whereas the number of trophoblast cells and the expression of HLA-G by trophoblast are similar in the decidua of PA and CP. We speculate that adequate numbers of uNK cells in the basal decidua are needed for normal expulsion of the placenta. Copyright © 2010 Elsevier Ltd. All rights reserved.

Presurgical mapping of basal cell carcinoma or squamous cell carcinoma by confocal laser endomicroscopy compared to traditional micrographic surgery: a single-centre prospective feasibility study.

PubMed

Schulz, Alexandra; Daali, Samira; Javed, Mehreen; Fuchs, Paul Christian; Brockmann, Michael; Igressa, Alhadi; Charalampaki, Patra

2016-12-01

At present, no ideal diagnostic tools exist in the market to excise cancer tissue with the required safety margins and to achieve optimal aesthetic results using tissue-conserving techniques. In this prospective study, confocal laser endomicroscopy (CLE) and the traditional gold standard of magnifying glasses (MG) were compared regarding the boundaries of in vivo basal cell carcinoma and squamous cell carcinoma. Tumour diameters defined by both methods were measured and compared with those determined by histopathological examination. Nineteen patients were included in the study. The CLE technique was found to be superior to excisional margins based on MG only. Re-excision was required in 68% of the cases following excision based on MG evaluation, but only in 27% of the cases for whom excision margins were based on CLE. Our results are promising regarding the distinction between tumour and healthy surrounding tissue, and indicate that presurgical mapping of basal cell carcinoma and squamous cell carcinoma is possible. The tool itself should be developed further with special attention to early detection of skin cancer.

Kinetics of the maintenance of the epidermis

NASA Astrophysics Data System (ADS)

Zhdanov, Vladimir P.; Cho, Nam-Joon

2013-08-01

The epidermis is the outermost layer of skin. It is comprised of keratin-containing cells called keratinocytes. Functionally, the epidermis serves as a physical barrier that can prevent infection and regulate body hydration. Maintenance and repair of the epidermis are important for human health. Mechanistically, these processes occur primarily via proliferation and differentiation of stem cells located in the basal monolayer. These processes are believed to depend on cell-cell communication and spatial constraints but existing kinetic models focus mainly on proliferation and differentiation. To address this issue, we present a mean-field kinetic model that takes these additional factors into account and describes the epidermis at a biosystem level. The corresponding equations operate with the populations of stem cells and differentiated cells in the basal layer. The keratinocytes located above the basal layer are treated at a more coarse-grained level by considering the thickness of the epidermis. The model clarifies the likely role of various negative feedbacks that may control the epidermis and, accordingly, provides insight into the cellular mechanisms underlying complex biological phenomena such as wound healing.

Paracrine Met signaling triggers epithelial–mesenchymal transition in mammary luminal progenitors, affecting their fate

PubMed Central

Di-Cicco, Amandine; Petit, Valérie; Chiche, Aurélie; Bresson, Laura; Romagnoli, Mathilde; Orian-Rousseau, Véronique; Vivanco, Maria dM; Medina, Daniel; Faraldo, Marisa M; Glukhova, Marina A; Deugnier, Marie-Ange

2015-01-01

HGF/Met signaling has recently been associated with basal-type breast cancers, which are thought to originate from progenitor cells residing in the luminal compartment of the mammary epithelium. We found that ICAM-1 efficiently marks mammary luminal progenitors comprising hormone receptor-positive and receptor-negative cells, presumably ductal and alveolar progenitors. Both cell populations strongly express Met, while HGF is produced by stromal and basal myoepithelial cells. We show that persistent HGF treatment stimulates the clonogenic activity of ICAM1-positive luminal progenitors, controlling their survival and proliferation, and leads to the expression of basal cell characteristics, including stem cell potential. This is accompanied by the induction of Snai1 and Snai2, two major transcription factors triggering epithelial–mesenchymal transition, the repression of the luminal-regulatory genes Elf5 and Hey1, and claudin down-regulation. Our data strongly indicate that paracrine Met signaling can control the function of luminal progenitors and modulate their fate during mammary development and tumorigenesis. DOI: http://dx.doi.org/10.7554/eLife.06104.001 PMID:26165517

Circulating basal anti-Müllerian hormone levels as predictor of ovarian response in women undergoing ovarian stimulation for in vitro fertilization.

PubMed

Nardo, Luciano G; Gelbaya, Tarek A; Wilkinson, Hannah; Roberts, Stephen A; Yates, Allen; Pemberton, Phil; Laing, Ian

2009-11-01

To evaluate the clinical value of basal anti-Müllerian hormone (AMH) measurements compared with other available determinants, apart from chronologic age, in the prediction of ovarian response to gonadotrophin stimulation. Prospective cohort study. Tertiary referral center for reproductive medicine and an IVF unit. Women undergoing their first cycle of controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). Basal levels of FSH and AMH as well as antral follicle count (AFC) were measured in 165 subjects. All patients were followed prospectively and their cycle outcomes recorded. Predictive value of FSH, AMH, and AFC for extremes of ovarian response to stimulation. Out of the 165 women, 134 were defined as normal responders, 15 as poor responders, and 16 as high responders. Subjects in the poor response group were significantly older then those in the other two groups. Anti-Müllerian hormone levels and AFC were markedly raised in the high responders and decreased in the poor responders. Compared with FSH and AFC, AMH performed better in the prediction of excessive response to ovarian stimulation-AMH area under receiver operating characteristic curve (ROC(AUC)) 0.81, FSH ROC(AUC) 0.66, AFC ROC(AUC) 0.69. For poor response, AMH (ROC(AUC) 0.88) was a significantly better predictor than FSH (ROC(AUC) 0.63) but not AFC (ROC(AUC) 0.81). AMH prediction of ovarian response was independent of age and PCOS. Anti-Müllerian hormone cutoffs of >3.75 ng/mL and <1.0 ng/mL would have modest sensitivity and specificity in predicting the extremes of response. Circulating AMH has the ability to predict excessive and poor response to stimulation with exogenous gonadotrophins. Overall, this biomarker is superior to basal FSH and AFC, and has the potential to be incorporated in to work-up protocols to predict patient's ovarian response to treatment and to individualize strategies aiming at reducing the cancellation rate and the iatrogenic complications of COH.

Contributions of PTCH Gene Variants to Isolated Cleft Lip and Palate

PubMed Central

Mansilla, M.A.; Cooper, M.E.; Goldstein, T.; Castilla, E.E.; Camelo, J.S. Lopez; Marazita, M.L.; Murray, J.C.

2007-01-01

Objective Mutations in patched (PTCH) cause the nevoid basal cell carcinoma syndrome (NBCCS), or Gorlin syndrome. Nevoid basal cell carcinoma syndrome may present with developmental anomalies, including rib and craniofacial abnormalities, and predisposes to several tumor types, including basal cell carcinoma and medulloblastoma. Cleft palate is found in 4% of individuals with nevoid basal cell carcinoma syndrome. Because there might be specific sequence alterations in PTCH that limit expression to orofacial clefting, a genetic study of PTCH was undertaken in cases with cleft lip and/or palate (CL/P) known not to have nevoid basal cell carcinoma syndrome. Results Seven new normal variants spread along the entire gene and three missense mutations were found among cases with cleft lip and/or palate. One of these variants (P295S) was not found in any of 1188 control samples. A second variant was found in a case and also in 1 of 1119 controls. The third missense (S827G) was found in 5 of 1369 cases and in 5 of 1104 controls and is likely a rare normal variant. Linkage and linkage desequilibrium also was assessed using normal variants in and adjacent to the PTCH gene in 220 families (1776 individuals), each with two or more individuals with isolated clefting. Although no statistically significant evidence of linkage (multipoint HLOD peak = 2.36) was uncovered, there was borderline evidence of significant transmission distortion for one haplotype of two single nucleotide polymorphisms located within the PTCH gene (p = .08). Conclusion Missense mutations in PTCH may be rare causes of isolated cleft lip and/or palate. An as yet unidentified variant near PTCH may act as a modifier of cleft lip and/or palate. PMID:16405370

Invasive urothelial carcinoma exhibiting basal cell immunohistochemical markers: A variant of urothelial carcinoma associated with aggressive features.

PubMed

Mai, Kien T; Truong, Luan D; Ball, Christopher G; Williams, Phillip; Flood, Trevor A; Belanger, Eric C

2015-08-01

We characterize invasive urothelial carcinoma (UC) exhibiting urothelial basal cell immunohistochemical markers. Consecutive invasive UCs were immunostained with CK20 and urothelial basal cell markers, cytokeratin 5 (CK5)/CD44. Immunostaining for CK5 and CD44 was scored as follows: positive for staining of more than 25% thickness of the epithelial nest or epithelium and low for lesser immunoreactivity. Invasive urothelial carcinoma (UC) exhibiting positive CK5/CD44 staining was designated as basal-like UC (BUC). In this study, of 251 invasive UC (pT1 in 57% and pT2-4 in 43%), BUC accounted for 40% of cases (accounting for most pT2-4 UC) and often presented as non-papillary UC without previous history of UC. In addition, BUC exhibited uniform nuclei with lesser degree of atypia than non BUC and decreased or negative cytokeratin 20 reactivity. Nested and microcystic variants of UC immunohistochemically stained as BUCs. Invasive non-BUCs were often papillary with marked cytologic atypia and pleomorphism, and accounted for most pT1 UC. The rates of perivesical invasion, lymph node and distant metastases were higher for BUC than non-BUC. All nine cases with absent/minimal residual in situ UC in 102 radical cystectomy specimens were from invasive non-BUC. BUC is distinguished from non-BUC due to this aggressive behavior, distinct immunohistochemical profile, and predominant non-papillary architecture. Our findings are consistent with recent studies identifying a subtype of muscle-invasive UC with molecular expression of basal cell and luminal cell molecular profiles. Our study further supports categorizing invasive UCs into these subtypes with different biological behaviors, possibly contributing to better therapeutic strategies. Copyright © 2015 Elsevier GmbH. All rights reserved.

Computer vision approach to morphometric feature analysis of basal cell nuclei for evaluating malignant potentiality of oral submucous fibrosis.

PubMed

Muthu Rama Krishnan, M; Pal, Mousumi; Paul, Ranjan Rashmi; Chakraborty, Chandan; Chatterjee, Jyotirmoy; Ray, Ajoy K

2012-06-01

This research work presents a quantitative approach for analysis of histomorphometric features of the basal cell nuclei in respect to their size, shape and intensity of staining, from surface epithelium of Oral Submucous Fibrosis showing dysplasia (OSFD) to that of the Normal Oral Mucosa (NOM). For all biological activity, the basal cells of the surface epithelium form the proliferative compartment and therefore their morphometric changes will spell the intricate biological behavior pertaining to normal cellular functions as well as in premalignant and malignant status. In view of this, the changes in shape, size and intensity of staining of the nuclei in the basal cell layer of the NOM and OSFD have been studied. Geometric, Zernike moments and Fourier descriptor (FD) based as well as intensity based features are extracted for histomorphometric pattern analysis of the nuclei. All these features are statistically analyzed along with 3D visualization in order to discriminate the groups. Results showed increase in the dimensions (area and perimeter), shape parameters and decreasing mean nuclei intensity of the nuclei in OSFD in respect to NOM. Further, the selected features are fed to the Bayesian classifier to discriminate normal and OSFD. The morphometric and intensity features provide a good sensitivity of 100%, specificity of 98.53% and positive predicative accuracy of 97.35%. This comparative quantitative characterization of basal cell nuclei will be of immense help for oral onco-pathologists, researchers and clinicians to assess the biological behavior of OSFD, specially relating to their premalignant and malignant potentiality. As a future direction more extensive study involving more number of disease subjects is observed.

Geomicrobiology of basal ice in a temperate glacier: implications for primary microbial production and export, elemental cycling and soil formation

NASA Astrophysics Data System (ADS)

Toubes-Rodrigo, Mario; Potgieter-Vermaak, Sanja; Sen, Robin; Elliott, David R.; Cook, Simon J.

2017-04-01

Basal ice is a significant sub-glacial component of glaciers and ice sheets that arises from ice-bedrock/substrate interaction. As a result, basal ice of a glacier retains a distinctive physical and chemical signature characterised by a high sediment- and low bubble-content and selective ionic enrichment. Previous research concluded that sediment entrapped in the basal ice matrix originates from the bedrock/substrate, and harbours an active microbial community. However, the nature and significance of the microbial community inhabiting basal ice facies remains poorly characterised. This paper reports on an integrated chemical, mineralogical, and microbial community analysis of basal ice in the subglacial environment at Svínafellsjökull, in south-east Iceland. Basal ice sediment supported 10E7 cells g^-1 and, based on glacier velocity and sediment flux, an estimated 10E17 cells a^-1 are exported to the glacier foreland. Furthermore, 16S rRNA gene analysis highlighted a glacier basal ice bacterial community dominated by Proteobacteria, Acidobacteria, Actinobacteria, and Chloroflexi. Sequences ascribed to chemolithotrophic-related species (Thiobacillus, Syderoxidans) were highly abundant. Minerological analyses of basal ice sediment confirmed dominant silicates and iron-containing minerals that represent susceptible substrates open to oxidation by the aforementioned chemolithotrophs. Previous studies have suggested that basal ice could constitute a good analogue for astrobiology. Svínafellsjökull and Mars geology are similar - volcanically derived rocks with a high abundance of silicates and iron-rich minerals, reinforcing this idea. Understanding where the limits of life in extreme environments, such as debris-rich basal ice, could help to unravel how life on other planets could succeed, and could help to identify which markers to use in order to find it. In dark and isolated basal ice niches, the dominating chemolithotrophic bacterial community are likely to act as primary producers, fixing carbon while weathering minerals and thus providing a plausible mechanism to explain how a basal ice microbial ecosystem can be sustained.

Laser scanning in vivo confocal microscopy of the normal human corneoscleral limbus.

PubMed

Patel, Dipika V; Sherwin, Trevor; McGhee, Charles N J

2006-07-01

To elucidate the structure of the human corneoscleral limbus by in vivo laser scanning confocal microscopy and to correlate limbal epithelial dimensions and density with the central epithelium and in relation to age. Fifty adult subjects were recruited into one of two age groups: younger (age<45 years) and older (age>or=45 years). Fifty left eyes of these 50 healthy subjects were examined by laser scanning in vivo confocal microscopy, to assess the basal epithelium of the central cornea and inferior limbus. Mean epithelial cell diameter, area, and density were calculated for the central basal epithelium, limbus-corneal basal epithelium, and limbus-palisade epithelium. Data were analyzed in relation to the two age groups, group A, 30+/-6 years (n=25; mean+/-SD), and group B, 60+/-11 years (n=25; P<0.01). Mean epithelial density in the limbus-cornea and limbus-palisade regions decreased significantly with age: limbus-cornea group A=7253+/-1077 cells/mm2 group B=6614+/-987 cells/mm2, P=0.03; limbus palisade group A=5409+/-799 cells/mm2, group B=5055+/-722 cells/mm2, P=0.03). Central corneal epithelial density did not change with age: group A=6162+/-503 cells/mm2, group B=6362+/-614 cells/mm2, P=0.08. Mean epithelial density was greatest at the limbus-cornea (7010+/-1081 cells/mm2) and lowest at the limbus-palisades (5289+/-847 cells/mm2). The mean width of palisade ridges was 25.0+/-6.3 microm. This is the first study to image clearly the living human corneal limbus by laser scanning in vivo confocal microscopy and to demonstrate quantitative changes in the basal epithelium with age.

Inhibition of RHO-ROCK signaling enhances ICM and suppresses TE characteristics through activation of Hippo signaling in the mouse blastocyst

PubMed Central

Kono, Kanako; Tamashiro, Dana Ann A.; Alarcon, Vernadeth B.

2014-01-01

Specification of the trophectoderm (TE) and inner cell mass (ICM) lineages in the mouse blastocyst correlates with cell position, as TE derives from outer cells whereas ICM from inner cells. Differences in position are reflected by cell polarization and Hippo signaling. Only in outer cells, the apical-basal cell polarity is established, and Hippo signaling is inhibited in such a manner that LATS1 and 2 (LATS1/2) kinases are prevented from phosphorylating YAP, a key transcriptional co-activator of the TE-specifying gene Cdx2. However, the molecular mechanisms that regulate these events are not fully understood. Here, we showed that inhibition of RHO-ROCK signaling enhances ICM and suppresses TE characteristics through activation of Hippo signaling and disruption of apical-basal polarity. Embryos treated with ROCK inhibitor Y-27632 exhibited elevated expression of ICM marker NANOG and reduced expression of CDX2 at the blastocyst stage. Y-27632-treated embryos failed to accumulate YAP in the nucleus, although it was rescued by concomitant inhibition of LATS1/2. Segregation between apical and basal polarity regulators, namely PARD6B, PRKCZ, SCRIB, and LLGL1, was dampened by Y-27632 treatment, whereas some of the polarization events at the late 8-cell stage such as compaction and apical localization of p-ERM and tyrosinated tubulin occurred normally. Similar abnormalities of Hippo signaling and apical-basal polarization were also observed in embryos that were treated with RHO GTPases inhibitor. These results suggest that RHO-ROCK signaling plays an essential role in regulating Hippo signaling and cell polarization to enable proper specification of the ICM and TE lineages. PMID:24997360

Evaluation of a Commercially Available Hyaluronic Acid Hydrogel (Restylane) as Injectable Scaffold for Dental Pulp Regeneration: An In Vitro Evaluation.

PubMed

Chrepa, Vanessa; Austah, Obadah; Diogenes, Anibal

2017-02-01

Regenerative endodontic procedures (REPs) are viable alternatives for treating immature teeth, yet these procedures do not predictably lead to pulp-dentin regeneration. A true bioengineering approach for dental pulp regeneration requires the incorporation of a scaffold conducive with the regeneration of the pulp-dentin complex. Several materials have been proposed as scaffolds for REPs; nonetheless, the majority are not eligible for immediate clinical chairside use. Thus, the aim of this study was to evaluate Restylane, a Food and Drug Administration-approved hyaluronic acid-based gel, as possible scaffold for REPs. Stem cells of the apical papilla (SCAP) were cultured either alone or in mixtures with either Restylane or Matrigel scaffolds. Groups were cultured in basal culture medium for 6, 24, and 72 hours, and cell viability was assessed. For the mineralizing differentiation experiments, groups were cultured in differentiation medium either for 7 days and processed for alkaline phosphatase activity or for 14 days and processed for gene expression by using quantitative reverse-transcription polymerase chain reaction. SCAP in basal medium served as control. Cell encapsulation in either Restylane or Matrigel demonstrated reduced cell viability compared with control. Nonetheless, cell viability significantly increased in the Restylane group in the course of 3 days, whereas it decreased significantly in the Matrigel group. Restylane promoted significantly greater alkaline phosphatase activity and upregulation of dentin sialophosphoprotein, dentin matrix acidic phosphoprotein-1, and matrix extracellular phosphoglycoprotein, compared with control. A Food and Drug Administration-approved hyaluronic acid-based injectable gel promoted SCAP survival, mineralization, and differentiation into an odontoblastic phenotype and may be a promising scaffold material for REPs. Published by Elsevier Inc.

Caveolin-1 expression as a prognostic marker in triple negative breast cancers of Asian women.

PubMed

Yeong, Joe; Thike, Aye Aye; Ikeda, Murasaki; Lim, Jeffrey Chun Tatt; Lee, Bernett; Nakamura, Seigo; Iqbal, Jabed; Tan, Puay Hoon

2018-02-01

Triple-negative breast cancers (TNBCs) are defined by their lack of oestrogen receptor, progesterone receptor and epidermal growth factor receptor 2. Although heterogeneous, the majority are aggressive and treatment options are limited. Caveolin acts as tumour suppressor or promoter depending on the cancer type. In this study, we aimed to determine if the expression levels of the candidate biomarker caveolin-1 on stromal or tumour cells were associated with clinicopathological parameters and disease outcomes in TNBCs from an ethnically diverse cohort of Asian women. Tumour specimens from 699 women with TNBC were subjected to immunohistochemical analysis of the frequency and intensity of caveolin-1 expression in tumour and stromal cells. A subset of 141 tumour samples also underwent Nanostring measurement of CAV1 mRNA. Results were correlated with clinicopathological parameters and disease outcomes. Expression of caveolin-1 in stromal cells was observed in 14.4% of TNBC cases. TNBCs of the basal-like phenotype (85% of samples) were significantly more likely to exhibit stromal cell caveolin-1 expression (p=0.028), as were those with a trabecular growth pattern (p=0.007). Lack of stromal caveolin-1 expression in both TNBCs and those with the basal-like phenotype was significantly associated with worse overall survival (p=0.009 and p=0.026, respectively): accordingly, increasing mRNA levels of CAV1 in TNBC samples predicted better overall survival. Caveolin-1 expression on TNBC tumour cells was not associated with clinical outcome. Stromal, but not tumoural, caveolin-1 expression is significantly associated with survival in Asian women with TNBC. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Total numbers of neurons and glial cells in cortex and basal ganglia of aged brains with Down syndrome--a stereological study.

PubMed

Karlsen, Anna Schou; Pakkenberg, Bente

2011-11-01

The total numbers of neurons and glial cells in the neocortex and basal ganglia in adults with Down syndrome (DS) were estimated with design-based stereological methods, providing quantitative data on brains affected by delayed development and accelerated aging. Cell numbers, volume of regions, and densities of neurons and glial cell subtypes were estimated in brains from 4 female DS subjects (mean age 66 years) and 6 female controls (mean age 70 years). The DS subjects were estimated to have about 40% fewer neocortical neurons in total (11.1 × 10(9) vs. 17.8 × 10(9), 2p ≤ 0.001) and almost 30% fewer neocortical glial cells with no overlap to controls (12.8 × 10(9) vs. 18.2 × 10(9), 2p = 0.004). In contrast, the total number of neurons in the basal ganglia was the same in the 2 groups, whereas the number of oligodendrocytes in the basal ganglia was reduced by almost 50% in DS (405 × 10(6) vs. 816 × 10(6), 2p = 0.01). We conclude that trisomy 21 affects cortical structures more than central gray matter emphasizing the differential impairment of brain development. Despite concomitant Alzheimer-like pathology, the neurodegenerative outcome in a DS brain deviates from common Alzheimer disease.

Using an AMACR (P504S)/34betaE12/p63 cocktail for the detection of small focal prostate carcinoma in needle biopsy specimens.

PubMed

Jiang, Zhong; Li, Cuizhen; Fischer, Andrew; Dresser, Karen; Woda, Bruce A

2005-02-01

We assessed the usefulness of immunohistochemical analysis with a 3-antibody cocktail (alpha-methylacyl coenzyme A racemase [AMACR, or P504S], 34betaE12, p63) and a double-chromogen reaction for detection of limited prostate cancer in 138 needle biopsy specimens, including 82 with small foci of prostatic adenocarcinoma and 56 benign prostates. When carcinoma was present, red cytoplasmic granular staining (AMACR) in the malignant glands and cells and dark brown nuclear (p63) and cytoplasmic (34betaE12) staining in basal cells of adjacent nonmalignant glands were found. Of 82 cases of small foci of prostatic adenocarcinoma, 78 (95%) expressed AMACR; all malignant glands were negative for basal cell staining. All benign glands adjacent to malignant glands were recognized easily by basal cell marker positivity and little or no AMACR expression. No benign glands were simultaneously positive for AMACR and negative for basal cell markers (specificity, 100%). There were no differences in intensity and numbers of positive glands with double-chromogen staining compared with using 1-color staining. Our results indicate that immunohistochemistry with a 3-antibody cocktail and double chromogen is a simple and easy assay that can be used as a routine test, which overcomes the problems of studying small lesions in prostate needle biopsies with multiple immunohistochemical stains.

New Perspectives in the Pharmacological Treatment of Non-Melanoma Skin Cancer.

PubMed

Savoia, Paola; Cremona, Ottavio; Fava, Paolo

2016-01-01

Non-melanoma skin cancers are the most common malignancy in humans, with a basal/squamous cell carcinoma incidence ratio of 4:1 in immunocompetent patients. Basal cell carcinoma rarely metastasizes but commonly causes significant local tissue destruction and disfigurement, whereas squamous cell carcinoma is associated with a substantial risk of recurrence and metastasis; the prognosis in metastatic patients is poor. Surgical approaches give a cure rate greater than 90% if appropriately applied, on the basis of the characteristics of the primary tumors and of the patients, but in selected cases, medical treatment (5-fluorouracil, imiquimod, diclofenac and, more recently, ingenol mebutate) is preferable to invasive procedures and provides a good chance of cure, with generally excellent cosmetic outcomes. In case of advanced and metastatic non-melanoma skin cancer, newly developed molecularly targeted therapy represents a reasonably promising alternative to classical cytostatics. In particular, the monoclonal antibody cetuximab, directed against the epidermal growth factor receptor, is effective and well-tolerated in squamous cell carcinoma patients. Moreover, the recent identification of mutations in the Hedgehog signaling pathway in basal cell carcinoma lead to the development of the smoothened Hedgehog pathway inhibitor vismodegib, that was recently approved for the treatment of locally advanced or metastatic basal cell carcinoma. In this review we provide an overview of the molecular pathways involved in NMSC pathogenesis, focusing on the mechanisms of action, indications, efficacy, side effects and contraindications of new medical treatments that specifically tackle molecular targets of these pathways.

Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome). Case report.

PubMed

Fini, G; Belli, E; Mici, E; Virciglio, P; Moricca, L M; D'Itri, L; Leonardi, A; Malavenda, M S; Krizzuk, D; Merola, R; Maturo, A; Pasta, V

2013-01-01

Gorlin-Goltz syndrome or nevoid basal cell carcinoma syndrome (NBCCS) comprises multiple basal cell carcinomas, keratocysts of the jaw, palmar/plantar pits, spine and rib anomalies, calcifications of the falx cerebri etc. The diagnosis is made according to clinical criteria (Kimonis Criteria) and genetic ones. We studied one family where father and then his sun resulted affected by each syndrome. Gorlin-Goltz syndrome is a rare disease diagnosed according to clinical criteria sometimes difficult to integrate. The family case we presented shows how you can get diagnosis even in older age and after numerous surgeries. Patients should be given special attention and therefore should be monitorized and need multidisciplinary treatments continued in time, even a trivial change of signs and symptoms may be an important indicator of a precipitating event which puts the patient's life under threat.

Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome). Case report

PubMed Central

FINI, G.; BELLI, E.; MICI, E.; VIRCIGLIO, P.; MORICCA, L.M.; D’ITRI, L.; LEONARDI, A.; MALAVENDA, M.S.; KRIZZUK, D.; MEROLA, R.; MATURO, A.; PASTA, V.

2013-01-01

Summary: Gorlin-Goltz syndrome or nevoid basal cell carcinoma syndrome (NBCCS) comprises multiple basal cell carcinomas, keratocysts of the jaw, palmar/plantar pits, spine and rib anomalies, calcifications of the falx cerebri etc. The diagnosis is made according to clinical criteria (Kimonis Criteria) and genetic ones. We studied one family where father and then his sun resulted affected by each syndrome. Gorlin-Goltz syndrome is a rare disease diagnosed according to clinical criteria sometimes difficult to integrate. The family case we presented shows how you can get diagnosis even in older age and after numerous surgeries. Patients should be given special attention and therefore should be monitorized and need multidisciplinary treatments continued in time, even a trivial change of signs and symptoms may be an important indicator of a precipitating event which puts the patient’s life under threat. PMID:23837959

Dynamic focus optical coherence tomography: feasibility for improved basal cell carcinoma investigation

NASA Astrophysics Data System (ADS)

Nasiri-Avanaki, M. R.; Aber, Ahmed; Hojjatoleslami, S. A.; Sira, Mano; Schofield, John B.; Jones, Carole; Podoleanu, A. Gh.

2012-03-01

Basal cell carcinoma (BCC) is the most common form of skin cancer. To improve the diagnostic accuracy, additional non-invasive methods of making a preliminary diagnosis have been sought. We have implemented an En-Face optical coherence tomography (OCT) for this study in which the dynamic focus was integrated into it. With the dynamic focus scheme, the coherence gate moves synchronously with the peak of confocal gate determined by the confocal interface optics. The transversal resolution is then conserved throughout the depth range and an enhanced signal is returned from all depths. The Basal Cell Carcinoma specimens were obtained from the eyelid a patient. The specimens under went analysis by DF-OCT imaging. We searched for remarkable features that were visualized by OCT and compared these findings with features presented in the histology slices.

Combined empirical mode decomposition and texture features for skin lesion classification using quadratic support vector machine.

PubMed

Wahba, Maram A; Ashour, Amira S; Napoleon, Sameh A; Abd Elnaby, Mustafa M; Guo, Yanhui

2017-12-01

Basal cell carcinoma is one of the most common malignant skin lesions. Automated lesion identification and classification using image processing techniques is highly required to reduce the diagnosis errors. In this study, a novel technique is applied to classify skin lesion images into two classes, namely the malignant Basal cell carcinoma and the benign nevus. A hybrid combination of bi-dimensional empirical mode decomposition and gray-level difference method features is proposed after hair removal. The combined features are further classified using quadratic support vector machine (Q-SVM). The proposed system has achieved outstanding performance of 100% accuracy, sensitivity and specificity compared to other support vector machine procedures as well as with different extracted features. Basal Cell Carcinoma is effectively classified using Q-SVM with the proposed combined features.

Characterization of basal and lipopolysaccharide-induced microRNA expression in equine peripheral blood mononuclear cells using Next-Generation Sequencing

PubMed Central

Buechner-Maxwell, Virginia A.; Witonsky, Sharon G.; Pleasant, R. Scott; Werre, Stephen R.; Ahmed, S. Ansar

2017-01-01

The innate immune response to lipopolysaccharide contributes substantially to the morbidity and mortality of gram-negative sepsis. Horses and humans share an exquisite sensitivity to lipopolysaccharide and thus the horse may provide valuable comparative insights into this aspect of the inflammatory response. MicroRNAs, small non-coding RNA molecules acting as post-transcriptional regulators of gene expression, have key roles in toll-like receptor signaling regulation but have not been studied in this context in horses. The central hypothesis of this study was that lipopolysaccharide induces differential microRNA expression in equine peripheral blood mononuclear cells in a manner comparable to humans. Illumina Next Generation Sequencing was used to characterize the basal microRNA transcriptome in isolated peripheral blood mononuclear cells from healthy adult horses, and to evaluate LPS-induced changes in microRNA expression in cells cultured for up to four hours. Selected expression changes were validated using quantitative reverse-transcriptase PCR. Only miR-155 was significantly upregulated by LPS, changing in parallel with supernatant tumor necrosis factor-α concentration. Eight additional microRNAs, including miR-146a and miR-146b, showed significant expression change with time in culture without a clear LPS effect. Target predictions indicated a number of potential immunity-associated targets for miR-155 in the horse, including SOCS1, TAB2 and elements of the PI3K signaling pathway, suggesting that it is likely to influence the acute inflammatory response to LPS. Gene alignment showed extensive conservation of the miR-155 precursor gene and associated promoter regions between horses and humans. The basal and LPS-stimulated microRNA expression pattern characterized here were similar to those described in human leukocytes. As well as providing a resource for further research into the roles of microRNAs in immune responses in horses, this will facilitate inter-species comparative study of the role of microRNAs in the inflammatory cascade during endotoxemia and sepsis. PMID:28552958

The many worlds hypothesis of dopamine prediction error: implications of a parallel circuit architecture in the basal ganglia.

PubMed

Lau, Brian; Monteiro, Tiago; Paton, Joseph J

2017-10-01

Computational models of reinforcement learning (RL) strive to produce behavior that maximises reward, and thus allow software or robots to behave adaptively [1]. At the core of RL models is a learned mapping between 'states'-situations or contexts that an agent might encounter in the world-and actions. A wealth of physiological and anatomical data suggests that the basal ganglia (BG) is important for learning these mappings [2,3]. However, the computations performed by specific circuits are unclear. In this brief review, we highlight recent work concerning the anatomy and physiology of BG circuits that suggest refinements in our understanding of computations performed by the basal ganglia. We focus on one important component of basal ganglia circuitry, midbrain dopamine neurons, drawing attention to data that has been cast as supporting or departing from the RL framework that has inspired experiments in basal ganglia research over the past two decades. We suggest that the parallel circuit architecture of the BG might be expected to produce variability in the response properties of different dopamine neurons, and that variability in response profile may not reflect variable functions, but rather different arguments that serve as inputs to a common function: the computation of prediction error. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of adenosine 5'-monophosphate on epidermal turnover.

PubMed

Furukawa, Fukumi; Kanehara, Shoko; Harano, Fumiki; Shinohara, Shigeo; Kamimura, Junko; Kawabata, Shigekatsu; Igarashi, Sachiyo; Kawamura, Mitsuaki; Yamamoto, Yuki; Miyachi, Yoshiki

2008-10-01

The structure and function of the epidermis is maintained by cell renewal based on epidermal turnover. Epidermal turnover is delayed by aging, and it is thought that the delay of the epidermal turnover is a cause of aging alternation of skin. The epidermal turnover is related to the energy metabolism of epidermal basal cells. Adenosine 5'-triphosphate (ATP) is needed for cell renewal: cell division, and adenosine 5'-monophosphate (AMP) increases the amount of intracellular ATP. These findings suggest that AMP accelerates the epidermal turnover delayed by aging. This study investigated whether AMP and adenosine 5'-monophosphate disodium salt (AMP2Na) accelerates the epidermal turnover. An effect of AMP2Na on cell proliferation was examined by our counting of keratinocytes. An effect of AMP2Na on cell cycle was examined by our counting of basal cells in DNA synthetic period of hairless rats. The effects of AMP2Na (or AMP) on the epidermal turnover were examined by our measuring stratum corneum transit time by use of guinea pigs, and by our measuring stratum corneum surface area by use of hairless rats and in a clinical pharmacological study. The AMP2Na showed two different profiles on the proliferation of primary cultured keratinocytes. At a low concentration it induced cell growth, whereas at a high concentration it inhibited cell growth. The number of basal cells in the DNA synthetic period of AMP2Na was significantly higher than that of the vehicle in hairless rats. The stratum corneum transit time of AMP2Na was significantly shorter than that of the vehicle in guinea pigs. The corneocyte surface area of emulsion containing AMP2Na was significantly smaller than that of the vehicle in volunteers. We conclude that AMP promotes the cell proliferation and the cell cycle progression of epidermal basal cells and accelerates epidermal turnover safely. In addition, AMP is useful for skin rejuvenation in dermatology and aesthetic dermatology.

Junction restructuring and spermatogenesis: the biology, regulation, and implication in male contraceptive development.

PubMed

Yan, Helen H N; Mruk, Dolores D; Cheng, C Yan

2008-01-01

Spermatogenesis that occurs in the seminiferous epithelium of adult mammalian testes is associated with extensive junction restructuring at the Sertoli-Sertoli cell, Sertoli-germ cell, and Sertoli-basement membrane interface. While this morphological phenomenon is known and has been described in great details for decades, the biochemical and molecular changes as well as the mechanisms/signaling pathways that define changes at the cell-cell and cell-matrix interface remain largely unknown until recently. In this chapter, we summarize and discuss findings in the field regarding the coordinated efforts of the anchoring [e.g., adherens junction (AJ), such as basal ectoplasmic specialization (basal ES)] and tight junctions (TJs) that are present in the same microenvironment, such as at the blood-testis barrier (BTB), or at distinctly opposite ends of the Sertoli cell epithelium, such as between apical ectoplasmic specialization (apical ES) in the apical compartment, and the BTB adjacent to the basal compartment of the epithelium. These efforts, in turn, regulate and coordinate different cellular events that occur during the seminiferous epithelial cycle. For instance, the events of spermiation and of preleptotene spermatocyte migration across the BTB both take place concurrently at stage VIII of the epithelial cycle of spermatogenesis. Recent findings suggest that these events are coordinated by protein complexes found at the apical and basal ES and TJ, which are located at different ends of the Sertoli cell epithelium. Besides, we highlight important areas of research that can now be undertaken, and functional studies that can be designed to tackle different issues pertinent to junction restructuring during spermatogenesis.

TFAP2C governs the luminal epithelial phenotype in mammary development and carcinogenesis.

PubMed

Cyr, A R; Kulak, M V; Park, J M; Bogachek, M V; Spanheimer, P M; Woodfield, G W; White-Baer, L S; O'Malley, Y Q; Sugg, S L; Olivier, A K; Zhang, W; Domann, F E; Weigel, R J

2015-01-22

Molecular subtypes of breast cancer are characterized by distinct patterns of gene expression that are predictive of outcome and response to therapy. The luminal breast cancer subtypes are defined by the expression of estrogen receptor-alpha (ERα)-associated genes, many of which are directly responsive to the transcription factor activator protein 2C (TFAP2C). TFAP2C participates in a gene regulatory network controlling cell growth and differentiation during ectodermal development and regulating ESR1/ERα and other luminal cell-associated genes in breast cancer. TFAP2C has been established as a prognostic factor in human breast cancer, however, its role in the establishment and maintenance of the luminal cell phenotype during carcinogenesis and mammary gland development have remained elusive. Herein, we demonstrate a critical role for TFAP2C in maintaining the luminal phenotype in human breast cancer and in influencing the luminal cell phenotype during normal mammary development. Knockdown of TFAP2C in luminal breast carcinoma cells induced epithelial-mesenchymal transition with morphological and phenotypic changes characterized by a loss of luminal-associated gene expression and a concomitant gain of basal-associated gene expression. Conditional knockout of the mouse homolog of TFAP2C, Tcfap2c, in mouse mammary epithelium driven by MMTV-Cre promoted aberrant growth of the mammary tree leading to a reduction in the CD24(hi)/CD49f(mid) luminal cell population and concomitant gain of the CD24(mid)/CD49f(hi) basal cell population at maturity. Our results establish TFAP2C as a key transcriptional regulator for maintaining the luminal phenotype in human breast carcinoma. Furthermore, Tcfap2c influences development of the luminal cell type during mammary development. The data suggest that TFAP2C has an important role in regulated luminal-specific genes and may be a viable therapeutic target in breast cancer.

African swine fever virus IAP-like protein induces the activation of nuclear factor kappa B.

PubMed

Rodríguez, Clara I; Nogal, María L; Carrascosa, Angel L; Salas, María L; Fresno, Manuel; Revilla, Yolanda

2002-04-01

African swine fever virus (ASFV) encodes a homologue of the inhibitor of apoptosis (IAP) that promotes cell survival by controlling the activity of caspase-3. Here we show that ASFV IAP is also able to activate the transcription factor NF-kappaB. Thus, transient transfection of the viral IAP increases the activity of an NF-kappaB reporter gene in a dose-responsive manner in Jurkat cells. Similarly, stably transfected cells expressing ASFV IAP have elevated basal levels of c-rel, an NF-kappaB-dependent gene. NF-kappaB complexes in the nucleus were increased in A224L-expressing cells compared with control cells upon stimulation with phorbol myristate acetate (PMA) plus ionomycin. This resulted in greater NF-kappaB-dependent promoter activity in ASFV IAP-expressing than in control cells, both in basal conditions and after PMA plus ionophore stimulation. The elevated NF-kappaB activity seems to be the consequence of higher IkappaB kinase (IKK) basal activity in these cells. The NF-kappaB-inducing activity of ASFV IAP was abrogated by an IKK-2 dominant negative mutant and enhanced by expression of tumor necrosis factor receptor-associated factor 2.

African Swine Fever Virus IAP-Like Protein Induces the Activation of Nuclear Factor Kappa B

PubMed Central

Rodríguez, Clara I.; Nogal, María L.; Carrascosa, Angel L.; Salas, María L.; Fresno, Manuel; Revilla, Yolanda

2002-01-01

African swine fever virus (ASFV) encodes a homologue of the inhibitor of apoptosis (IAP) that promotes cell survival by controlling the activity of caspase-3. Here we show that ASFV IAP is also able to activate the transcription factor NF-κB. Thus, transient transfection of the viral IAP increases the activity of an NF-κB reporter gene in a dose-responsive manner in Jurkat cells. Similarly, stably transfected cells expressing ASFV IAP have elevated basal levels of c-rel, an NF-κB-dependent gene. NF-κB complexes in the nucleus were increased in A224L-expressing cells compared with control cells upon stimulation with phorbol myristate acetate (PMA) plus ionomycin. This resulted in greater NF-κB-dependent promoter activity in ASFV IAP-expressing than in control cells, both in basal conditions and after PMA plus ionophore stimulation. The elevated NF-κB activity seems to be the consequence of higher IκB kinase (IKK) basal activity in these cells. The NF-κB-inducing activity of ASFV IAP was abrogated by an IKK-2 dominant negative mutant and enhanced by expression of tumor necrosis factor receptor-associated factor 2. PMID:11907233

Endotoxin-induced basal respiration alterations of renal HK-2 cells: A sign of pathologic metabolism down-regulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Quoilin, C., E-mail: cquoilin@ulg.ac.be; Mouithys-Mickalad, A.; Duranteau, J.

Highlights: Black-Right-Pointing-Pointer A HK-2 cells model of inflammation-induced acute kidney injury. Black-Right-Pointing-Pointer Two oximetry methods: high resolution respirometry and ESR spectroscopy. Black-Right-Pointing-Pointer Oxygen consumption rates of renal cells decrease when treated with LPS. Black-Right-Pointing-Pointer Cells do not recover normal respiration when the LPS treatment is removed. Black-Right-Pointing-Pointer This basal respiration alteration is a sign of pathologic metabolism down-regulation. -- Abstract: To study the mechanism of oxygen regulation in inflammation-induced acute kidney injury, we investigate the effects of a bacterial endotoxin (lipopolysaccharide, LPS) on the basal respiration of proximal tubular epithelial cells (HK-2) both by high-resolution respirometry and electron spin resonancemore » spectroscopy. These two complementary methods have shown that HK-2 cells exhibit a decreased oxygen consumption rate when treated with LPS. Surprisingly, this cellular respiration alteration persists even after the stress factor was removed. We suggested that this irreversible decrease in renal oxygen consumption after LPS challenge is related to a pathologic metabolic down-regulation such as a lack of oxygen utilization by cells.« less

A novel method of basal crevasse height estimation and subsequent rifting

NASA Astrophysics Data System (ADS)

Logan, L.; Catania, G. A.; Lavier, L. L.; Choi, E.

2012-12-01

Basal crevasses may play an important precursory role in the location and propagation of rifts and in ice shelf disintegration. Here we develop a novel method for estimating the locations and heights of basal crevasses formed at the grounding line of ice shelves and ice streams. We assume a thin-elastic beam formulation (TEB) with a tensional plastic yielding criterion to capture the physics of a tidally flexed grounding line. Observations of basal crevasses in the Siple Coast area match well with predictions produced by this method. Areas with large misfit can be delineated by examining the strain rate field; indeed, in our estimations those crevasses which deviate most from the TEB prediction lie directly in a shear margin. We test the method against other areas in the Larsen Ice Shelf, and find again a good match. Thus we suggest the TEB as an alternative to other crevasse estimation methods, as it produces a good fit in predominantly tensile regions, requires no tuning or prior information, and is computationally free to implement into large scale ice models which aim at physically simulating calving and fracture processes. We pursue modeling basal crevasses as they evolve with a thermomechanical finite-difference 3-dimensional model called SNAC. Viscoelastoplastic ice follows Mohr-Coulomb tension failure with Glen's flow law. We examine the conditions necessary for a basal crevasse formed on the downstream side of an ice rise to propagate the full thickness of the ice, developing into a rift.

DOR undergoes nucleo-cytoplasmic shuttling, which involves passage through the nucleolus.

PubMed

Mauvezin, Caroline; Sancho, Ana; Ivanova, Saska; Palacin, Manuel; Zorzano, Antonio

2012-09-21

DOR is a bi-functional protein that regulates transcription and enhances starvation-induced autophagy. While autophagy has been mostly described as a stress-response mechanism, cells also need autophagy to maintain homeostasis in basal conditions. However, the mechanisms regulating basal autophagy still remain unknown. Our results show that DOR acts in basal autophagy. Indeed, DOR already undergoes nucleo-cytoplasmic shuttling in basal conditions and, surprisingly, DOR exits continuously the nucleus and traverses the nucleolus. However, the nucleolus integrity is not essential for both DOR nucleo-cytoplasmic shuttling and DOR function on basal autophagy. Taken together, we propose that DOR exit from the nucleus is essential for basal autophagy stimulation even under nucleolus disruption. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Gorlin-goltz syndrome: a rare case.

PubMed

Ganguly, Satyaki; Jaykar, Kranti C; Kumar, Rajesh; Jha, Abhijeet Kumar; Banerjee, P K

2015-01-01

Gorlin-Goltz syndrome or nevoid basal cell carcinoma syndrome is characterized by multiple basocellular epitheliomas, keratocysts in the jaws, bifid ribs, palmar and/or plantar pits and ectopic calcifications of the falx cerebri. We describe a case of Gorlin-Goltz syndrome illustrating the importance of a thorough examination including the examination of palms and soles and detailed investigations in a patient having lesions suggestive of basal cell carcinoma and multiple naevi.

Gorlin-Goltz Syndrome: A Rare Case

PubMed Central

Ganguly, Satyaki; Jaykar, Kranti C; Kumar, Rajesh; Jha, Abhijeet Kumar; Banerjee, PK

2015-01-01

Gorlin-Goltz syndrome or nevoid basal cell carcinoma syndrome is characterized by multiple basocellular epitheliomas, keratocysts in the jaws, bifid ribs, palmar and/or plantar pits and ectopic calcifications of the falx cerebri. We describe a case of Gorlin-Goltz syndrome illustrating the importance of a thorough examination including the examination of palms and soles and detailed investigations in a patient having lesions suggestive of basal cell carcinoma and multiple naevi. PMID:25814758

Monoclonal antibody (AFH1) immunoreactive on morphologically abnormal basal melanocytes within dysplastic nevi, nevocellular nevus nests, and melanoma.

PubMed

Aronson, P J; Ito, K; Fukaya, T; Hashimoto, K; Mehregan, A H

1988-04-01

The mouse monoclonal antibody AFH1 was produced using formalin-fixed, sham paraffin-embedded human melanoma cell culture line A375 as immunogen. Reactivity of this antibody was assessed by immunohistochemical techniques against formalin- or acid alcohol-fixed paraffin-embedded tissue as well as formalin- or acid alcohol-fixed unembedded lesions. Ninety-seven nevomelanocytic lesions, neurofibromas, epithelial lesions, and a plasmacellular infiltrate were evaluated. AFH1 was immunoreactive on 54 of 55 nevocytic lesions (98.2%), 15 of 16 primary melanomas (93.7%), a lentigo maligna, and nests in 21 of 21 dysplastic nevi (100%). Of 100 consecutive basal melanocytes of intraepidermal melanoma cells counted in each lesion, mean AFH1 immunoreactivity for nonnested basal melanocytes in nevocellular nevi was 3.8%; for dysplastic nevi, 13.8%; and for intraepidermal melanoma cells, 78.0%. When nonnested basal melanocytes were subdivided into cytologically normal and abnormal cell groups, AFH1 immunoreactivity was 9.4% and 72.6%, respectively. AFH1 recognition of the lentiginous portion of dysplastic nevi corresponds statistically to the appearance of abnormal melanocyte cytology, nest formation, or both. Using 50% immunoreactive nonnested melanocytes as the criterion, AFH1 seems to distinguish primary melanoma from dysplastic nevi with a sensitivity of 93.8% and a specificity of 95.8%.

The Centrioles, Centrosomes, Basal Bodies, and Cilia of Drosophila melanogaster

PubMed Central

Lattao, Ramona; Kovács, Levente; Glover, David M.

2017-01-01

Centrioles play a key role in the development of the fly. They are needed for the correct formation of centrosomes, the organelles at the poles of the spindle that can persist as microtubule organizing centers (MTOCs) into interphase. The ability to nucleate cytoplasmic microtubules (MTs) is a property of the surrounding pericentriolar material (PCM). The centriole has a dual life, existing not only as the core of the centrosome but also as the basal body, the structure that templates the formation of cilia and flagellae. Thus the structure and functions of the centriole, the centrosome, and the basal body have an impact upon many aspects of development and physiology that can readily be modeled in Drosophila. Centrosomes are essential to give organization to the rapidly increasing numbers of nuclei in the syncytial embryo and for the spatially precise execution of cell division in numerous tissues, particularly during male meiosis. Although mitotic cell cycles can take place in the absence of centrosomes, this is an error-prone process that opens up the fly to developmental defects and the potential of tumor formation. Here, we review the structure and functions of the centriole, the centrosome, and the basal body in different tissues and cultured cells of Drosophila melanogaster, highlighting their contributions to different aspects of development and cell division. PMID:28476861

Generalized arteriosclerosis and changes of the cochlea in young adults.

PubMed

Nomiya, Rie; Nomiya, Shigenobu; Kariya, Shin; Okano, Mitsuhiro; Morita, Norimasa; Cureoglu, Sebahattin; Schachern, Patricia A; Nishizaki, Kazunori; Paparella, Michael M

2008-12-01

To disclose the histopathologic findings of the cochlea in young adults with generalized arteriosclerosis. It is well known that arteriosclerosis begins and progresses during childhood. Although the relationship between arteriosclerosis and auditory function in elderly people was examined in many reports, the histopathologic effect of arteriosclerosis on the cochlea in young adults has not been studied. This study involved quantitative analysis, including the number of spiral ganglion cells, the loss of cochlear outer hair cells, and the areas of stria vascularis and spiral ligament. It included 10 temporal bones from 6 subjects with generalized arteriosclerosis and 10 age-matched normal control temporal bones from 7 subjects. The mean number of spiral ganglion cells in the cochlea with generalized arteriosclerosis was significantly lower than that in normal controls in the basal turn. The mean loss of outer hair cells in the cochlea with generalized arteriosclerosis was significantly greater than that of normal controls in the basal and apical turns. The stria vascularis and spiral ligament were severely atrophic, with generalized arteriosclerosis in the basal turn. There was no significant difference in the thickness of the spiral modiolar artery between generalized arteriosclerosis and normal controls. Degeneration of the cochlea, especially in the basal turn, was already apparent in young adults with generalized arteriosclerosis.

The infection of primary avian tracheal epithelial cells with infectious bronchitis virus

PubMed Central

Shen, Ching-I; Wang, Ching-Ho; Liao, Jiunn-Wang; Hsu, Tien-Wang; Kuo, Shu-Ming; Su, Hong-Lin

2009-01-01

Here we introduce a culture system for the isolation, passaging and amplification of avian tracheal epithelial (ATE) cells. The ATE medium, which contains chicken embryo extract and fetal bovine serum, supports the growth of ciliated cells, goblet cells and basal cells from chicken tracheas on fibronectin- or matrigel-coated dishes. Non-epithelial cells make up less than 10% of the total population. We further show that ATE cells support the replication and spread of infectious bronchitis virus (IBV). Interestingly, immunocytostaining revealed that basal cells are resistant to IBV infection. We also demonstrate that glycosaminoglycan had no effect on infection of the cells by IBV. Taken together, these findings suggest that primary ATE cells provide a novel cell culture system for the amplification of IBV and the in vitro characterization of viral cytopathogenesis. PMID:19793537

Embryonic mammary signature subsets are activated in Brca1-/- and basal-like breast cancers

PubMed Central

2013-01-01

Introduction Cancer is often suggested to result from development gone awry. Links between normal embryonic development and cancer biology have been postulated, but no defined genetic basis has been established. We recently published the first transcriptomic analysis of embryonic mammary cell populations. Embryonic mammary epithelial cells are an immature progenitor cell population, lacking differentiation markers, which is reflected in their very distinct genetic profiles when compared with those of their postnatal descendents. Methods We defined an embryonic mammary epithelial signature that incorporates the most highly expressed genes from embryonic mammary epithelium when compared with the postnatal mammary epithelial cells. We looked for activation of the embryonic mammary epithelial signature in mouse mammary tumors that formed in mice in which Brca1 had been conditionally deleted from the mammary epithelium and in human breast cancers to determine whether any genetic links exist between embryonic mammary cells and breast cancers. Results Small subsets of the embryonic mammary epithelial signature were consistently activated in mouse Brca1-/- tumors and human basal-like breast cancers, which encoded predominantly transcriptional regulators, cell-cycle, and actin cytoskeleton components. Other embryonic gene subsets were found activated in non-basal-like tumor subtypes and repressed in basal-like tumors, including regulators of neuronal differentiation, transcription, and cell biosynthesis. Several embryonic genes showed significant upregulation in estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and/or grade 3 breast cancers. Among them, the transcription factor, SOX11, a progenitor cell and lineage regulator of nonmammary cell types, is found highly expressed in some Brca1-/- mammary tumors. By using RNA interference to silence SOX11 expression in breast cancer cells, we found evidence that SOX11 regulates breast cancer cell proliferation and cell survival. Conclusions Specific subsets of embryonic mammary genes, rather than the entire embryonic development transcriptomic program, are activated in tumorigenesis. Genes involved in embryonic mammary development are consistently upregulated in some breast cancers and warrant further investigation, potentially in drug-discovery research endeavors. PMID:23506684

Dynamics of action potential backpropagation in basal dendrites of prefrontal cortical pyramidal neurons.

PubMed

Zhou, Wen-Liang; Yan, Ping; Wuskell, Joseph P; Loew, Leslie M; Antic, Srdjan D

2008-02-01

Basal dendrites of neocortical pyramidal neurons are relatively short and directly attached to the cell body. This allows electrical signals arising in basal dendrites to strongly influence the neuronal output. Likewise, somatic action potentials (APs) should readily propagate back into the basilar dendritic tree to influence synaptic plasticity. Two recent studies, however, determined that sodium APs are severely attenuated in basal dendrites of cortical pyramidal cells, so that they completely fail in distal dendritic segments. Here we used the latest improvements in the voltage-sensitive dye imaging technique (Zhou et al., 2007) to study AP backpropagation in basal dendrites of layer 5 pyramidal neurons of the rat prefrontal cortex. With a signal-to-noise ratio of > 15 and minimal temporal averaging (only four sweeps) we were able to sample AP waveforms from the very last segments of individual dendritic branches (dendritic tips). We found that in short- (< 150 microm) and medium (150-200 microm in length)-range basal dendrites APs backpropagated with modest changes in AP half-width or AP rise-time. The lack of substantial changes in AP shape and dynamics of rise is inconsistent with the AP-failure model. The lack of substantial amplitude boosting of the third AP in the high-frequency burst also suggests that in short- and medium-range basal dendrites backpropagating APs were not severely attenuated. Our results show that the AP-failure concept does not apply in all basal dendrites of the rat prefrontal cortex. The majority of synaptic contacts in the basilar dendritic tree actually received significant AP-associated electrical and calcium transients.

Using corneal confocal microscopy to track changes in the corneal layers of dry eye patients after autologous serum treatment.

PubMed

Mahelkova, Gabriela; Jirsova, Katerina; Seidler Stangova, Petra; Palos, Michalis; Vesela, Viera; Fales, Ivan; Jiraskova, Nada; Dotrelova, Dagmar

2017-05-01

In vivo corneal confocal microscopy allows the examination of each layer of the cornea in detail and the identification of pathological changes at the cellular level. The purpose of this study was to identify the possible effects of a three-month treatment with autologous serum eye-drops in different corneal layers of patients with severe dry eye disease using corneal confocal microscopy. Twenty-six patients with dry eye disease were included in the study. Corneal fluorescein staining was performed. The corneas of the right eyes were examined using in vivo corneal confocal microscopy before and after a three-month treatment with autologous serum drops. The densities of superficial and basal epithelial cells, Langerhans cells, the keratocytes and activated keratocytes, the density of endothelial cells and the status of the sub-basal nerve plexus fibres were evaluated. A significant decrease in corneal fluorescein staining was found after the three-month autologous serum treatment (p = 0.0006). The basal epithelial cell density decreased significantly (p = 0.001), while the density of superficial epithelial cells did not change significantly (p = 0.473) nor did the number of Langerhans cells or activated keratocytes (p = 0.223; p = 0.307, respectively). There were no differences in the other corneal cell layers or in the status of the nerve fibres. The results demonstrate the ability of corneal confocal microscopy to evaluate an improvement in the basal epithelial cell layer of the cornea after autologous serum treatment in patients with dry eye disease. More studies with longer follow-up periods are needed to elucidate the suitability of corneal confocal microscopy to follow the effect of autologous serum treatment on nerve fibres or other corneal layers in dry eye disease patients. © 2016 Optometry Australia.

Sas-4 proteins are required during basal body duplication in Paramecium

PubMed Central

Gogendeau, Delphine; Hurbain, Ilse; Raposo, Graca; Cohen, Jean; Koll, France; Basto, Renata

2011-01-01

Centrioles and basal bodies are structurally related organelles composed of nine microtubule (MT) triplets. Studies performed in Caenorhabditis elegans embryos have shown that centriole duplication takes place in sequential way, in which different proteins are recruited in a specific order to assemble a procentriole. ZYG-1 initiates centriole duplication by triggering the recruitment of a complex of SAS-5 and SAS-6, which then recruits the final player, SAS-4, to allow the incorporation of MT singlets. It is thought that a similar mechanism (that also involves additional proteins) is present in other animal cells, but it remains to be investigated whether the same players and their ascribed functions are conserved during basal body duplication in cells that exclusively contain basal bodies. To investigate this question, we have used the multiciliated protist Paramecium tetraurelia. Here we show that in the absence of PtSas4, two types of defects in basal body duplication can be identified. In the majority of cases, the germinative disk and cartwheel, the first structures assembled during duplication, are not detected. In addition, if daughter basal bodies were formed, they invariably had defects in MT recruitment. Our results suggest that PtSas4 has a broader function than its animal orthologues. PMID:21289083

Non-melanoma Skin Cancer in Canada Chapter 1: Introduction to the Guidelines.

PubMed

Guenther, Lyn C; Barber, Kirk; Searles, Gordon E; Lynde, Charles W; Janiszewski, Peter; Ashkenas, John

2015-01-01

Non-melanoma skin cancer (NMSC), including basal and squamous cell carcinoma, represents the most common malignancy. The aim of this document is to provide guidance to Canadian health care practitioners on NMSC management. After conducting a literature review, the group developed recommendations for prevention, management, and treatment of basal cell carcinomas, squamous cell carcinomas, and actinic keratoses. These tumour types are considered separately in the accompanying articles. The Grading of Recommendations Assessment, Development and Evaluation system was used to assign strength to each recommendation. This introduction describes the scope and structure of the guidelines and the methods used to develop them. The epidemiology of NMSC is reviewed, as are the pathophysiologic changes occurring with damage to the skin, which lead to the formation of actinic keratoses and invasive squamous or basal cell carcinomas. This introduction describes the need for primary prevention and offers an overview of treatment options that are discussed in later chapters of the guidelines. © The Author(s) 2015.

Immunoprevention of Basal Cell Carcinomas with Recombinant Hedgehog-interacting Protein

PubMed Central

Vogt, Annika; Chuang, Pao-Tien; Hebert, Jennifer; Hwang, Jimmy; Lu, Ying; Kopelovich, Levy; Athar, Mohammad; Bickers, David R.; Epstein, Ervin H.

2004-01-01

Basal cell carcinomas (BCCs) are driven by abnormal hedgehog signaling and highly overexpress several hedgehog target genes. We report here our use of one of these target genes, hedgehog-interacting protein (Hip1), as a tumor-associated antigen for immunoprevention of BCCs in Ptch1+/− mice treated with ionizing radiation. Hip1 mRNA is expressed in adult mouse tissues at levels considerably lower than those in BCCs. Immunization with either of two large recombinant Hip1 polypeptides was well tolerated in Ptch1+/− mice, induced B and T cell responses detectable by enzyme-linked immunosorbent assay, Western blot, delayed type hypersensitivity, and enzyme-linked immunospot assay, and reduced the number of BCCs by 42% (P < 0.001) and 32% (P < 0.01), respectively. We conclude that immunization with proteins specifically up-regulated by hedgehog signaling may hold promise as a preventive option for patients such as those with the basal cell nevus syndrome who are destined to develop large numbers of BCCs. PMID:15024045

Association of basal serum androgen levels with ovarian response and ICSI cycle outcome.

PubMed

Abide Yayla, C; Ozkaya, E; Kayatas Eser, S; Sanverdi, I; Devranoglu, B; Kutlu, T

2018-05-01

The purpose of this study was to assess the predictive value of basal serum testosterone (T) and dehydroepiandrosterone sulfate (DHEAS) levels during follicular phase for ovarian response and outcome in intracytoplasmic sperm injection (ICSI) cycles of women with diminished ovarian reserve. We prospectively gathered data of basal serum androgen levels and ICSI cycle characteristics of 120 women with diminished ovarian reserve. Association of basal serum T and DHEAS levels with ovarian response was analyzed. Basal T and DHEAS levels were similar between pregnant and non-pregnant cases (P > 0.05). There were significant differences between groups with and without successful embryo implantation in terms of serum follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), gonadotropin starting and total dose, and peak estradiol level (P < 0.05). There were 58 (49.2%) cases who did not reach to the embryo transfer stage due to several reasons including cancelation of stimulation due to unresponsiveness (n = 26, 21.7%), no oocyte at oocyte pickup (n = 11, 9.2%), no mature oocyte (n = 6, 5%), and failure of fertilization or embryo development (n = 15, 12.5%). Basal androgen levels were not significant predictors for any of the cycle outcome. AMH level was a significant predictor for failure of fertilization or embryo development (AUC 0.722, P = 0.01) and cancelation of stimulation (AUC 0.801, P < 0.001). FSH was a significant predictor for cancelation of stimulation (AUC 0.774, P < 0.001). In women with diminished ovarian reserve, basal T and DHEAS levels have no value in predicting any of the cycle outcome parameters.

Immunoexpression of P63 and SOX2 in triple-negative breast cancers, Indonesia

PubMed Central

Kamarlis, Reno K; Lubis, Muhammad ND; Hernowo, Bethy S; Kar, Azmi S

2018-01-01

Background: Using immunohistochemical stains to target specific breast cancer markers has become indispensable for evaluation of small diagnostic tissue specimens, and therefore novel marker cocktails for specific breast cancers are required. This study was conducted to assess the immunoexpression of P63 and SOX2 in triple negative breast cancer (TNBC), and to evaluate the predictive diagnostic value of these markers for specific types of TNBC. Methods: Histological slides and paraffin blocks of TNBC cases were collected from Dr. Hasan Sadikin Hospital, Bandung, Indonesia from 5-years period (2011-2015). Each histological slide was subjected to immunohistochemical staining for P63 (nucleus and cytoplasm) and SOX2 (nucleus), with specific primer antibodies. Immunoexpression of P63 and SOX2 was evaluated using immunoreactivity scoring. Associations between P63 and SOX2 immunoexpression and TNBC types were assessed using Mann Whitney tests. In addition, the predictive diagnostic values of these markers were assessed. Results: Forty TNBC histological slides were included, and 23 (57.5%) were Basal-like type TNBC and 17 (42.5%) were Non basal-like type TNBC. Immunoexpression of P63 nucleus and SOX2 was not different between types of TNBC. However, immunoexpression of P63 in the cytoplasm in Basal-like type TNBC was significantly higher than in Non basal-like type TNBC ( p=0.021). Predictor diagnostic value analysis suggested that immunoexpression of P63 in cytoplasm had 56.5% sensitivity and 70.6% specificity for diagnosing Basal-like type TNBC, with area under curve of 0.64.    Conclusions: Immunoexpression of P63 in the cytoplasm has a relatively weak diagnostic value to discriminate Basal-like and Non basal-like types of TNBC. PMID:29527291

Jacalin and peanut agglutinin (PNA) bindings in the taste bud cells of the rat: new reliable markers for type IV cells of the rat taste buds.

PubMed

Taniguchi, Ryo; Shi, Lei; Fujii, Masae; Ueda, Katsura; Honma, Shiho; Wakisaka, Satoshi

2005-12-01

Lectin histochemistry of Jacalin (Artocarpus integrifolia) and peanut agglutinin (PNA), specific lectins for galactosyl (beta-1, 3) N-acetylgalactosamine (galactosyl (beta-1, 3) GalNAc), was applied to the gustatory epithelium of the adult rat. In the ordinary lingual epithelium, Jacalin and PNA labeled the cell membrane from the basal to granular cell layer. They also bound membranes of rounded-cells at the basal portion of taste buds, but the number of PNA labeled cells was smaller than that of Jacalin labeled cells. There was no apparent difference in the binding patterns of Jacalin and PNA among the taste buds of the lingual papillae and those of the palatal epithelium. Occasionally, a few spindle-shaped cells were labeled with Jacalin, but not with PNA. Double labeling of Jacalin and alpha-gustducin, a specific marker for type II cells, revealed that Jacalin-labeled spindle-shaped taste cells were immunonegative for alpha-gustducin. Spindle-shaped cells expressing protein gene product 9.5 (PGP 9.5) immunoreactivity lacked Jacalin labeling. During the development of taste buds in circumvallate papillae, the binding pattern of Jacalin became almost identical from postnatal day 5. The present results indicate that rounded cells at the basal portion of the taste buds cells (type IV cells) bind to Jacalin and PNA, and these lectins are specific markers for type IV cells of the rat taste cells.

[Immunohistochemical study of the specific features of expression of matrix metalloproteinases 1, 9 in the photoaged skin, the foci of actinic keratosis and basal cell carcinoma].

PubMed

Kuznetsova, E V; Snarskaya, E S; Zavalishina, L E; Tkachenko, S B

Matrix metalloproteinases (MMPs) mediate the degradation of all types of collagens and other extracellular matrix components (elastin, proteoglycans, and laminin), their synthesis and accumulation play a key role in the hydrolysis of basement membrane. MMPs are involved in a wide range of proteolytic processes in the presence of different physiological and pathological changes, including inflammation, wound healing, angiogenesis, and carcinogenesis. to study the specific features of MMP-1 and MMP-9 expression in different stages of skin photoaging, in the foci of actinic keratosis and basal cell carcinoma by immunohistochemical examination. 12 samples of the healthy skin (6 samples of the eyelid skin with Glogau grade II photoaging; 6 ones of eyelid skin with Glogau grades III-IV photoaging) and biopsies from 8 foci of actinic keratosis and from 8 ones of basal cell carcinoma were examined. A positive reaction to MMPs was shown as different brown staining intensity in the cytoplasm of keratinocytes/tumor cells. MMP-1 and MMP-9 expression was recorded in 67% of the histological specimens of the Glogau grade III photoaged skin and in 100% of those of Glogau grade IV. In the foci of actinic keratosis, the expression of MMP-1 was observed in 62.5% of cases and that of MMP-9 was seen in 87.5%. In basal cell carcinoma, the expression of MMP-1 and MMP-9 was detected in all investigated samples. The immunomorphological findings are indicative of the important role of the level of MMP-1 and MMP-9 expression that is associated with the degree of progression of skin photoaging processes. Minimal MMP-1 and MMP-9 expression was recorded even in grades III-IV photoaging and in the foci of actinic keratosis. Intense MMP-1 and MMP-9 expression was detected in malignant skin epithelial neoplasms as different clinicomorphological types of basal cell carcinoma.

Cell proliferation and p53 expression in pseudoepitheliomatous hyperplasia of oral paracoccidioidomycosis.

PubMed

Kaminagakura, E; Bonan, P R F; Lopes, M A; Almeida, O P

2006-09-01

Paracoccidioidomycosis (PCMycosis) is a systemic mycosis frequently found in many regions of Latin America. Microscopically, it is characterised by granulomatous inflammation and pseudoepitheliomatous hyperplasia (PEH). This work describes the proliferation index and p53 expression by immunohistochemistry in PEH of PCMycosis, normal oral mucosa (NOM) and mild oral epithelial dysplasia (ED). Ki67 positive cells were present in the basal and parabasal layers in NOM and PEH, while in ED it was also observed in the spinous layer. Percentage of ki67 positive cells was 7.7, 28.2 and 46.0 in NOM, PEH and ED respectively. p53 was negative in NOM and in PEH it was expressed by few cells in the basal layer of only three cases. However, it was expressed in all cases of ED, in basal and parabasal layers. Although histologically PEH mimics well-differentiated squamous cell carcinoma, its proliferative pattern and p53 expression are more similar to NOM than to dysplasia. These findings, confirm PEH as a reactive process probably associated with the underlying chronic inflammation.

Genetic and clinical predictors of ovarian response in assisted reproductive technology

NASA Astrophysics Data System (ADS)

Wiweko, B.; Damayanti, I.; Suryandari, D.; Natadisastra, M.; Pratama, G.; Sumapraja, K.; Meutia, K.; Iffanolia, P.; Harzief, A. K.; Hestiantoro, A.

2017-08-01

Several factors are known to influence ovarian response to rFSH stimulation such as age, antral follicle count (AFC), and basal FSH level, Mutation of allele Ser680Asn in FSHR gene was responsible to ovarian resistance toward exogenous FSH. The aim of this study is to develop a prediction model of ovarian response to COS in IVF. This study was a prospective cohort study. One hundred and thirteen women undergoing their first cycle of IVF in Yasmin IVF Clinic Jakarta were recruited to this study. Clinical datas included were age, BMI, and AFC. Basal FSH and E2 as well as serum AMH was measured from peripheral blood taken at second day of cycle. Bsr-1 enzyme is used to identify the polymorphism in exon 10 position 680 with RFLP technique. Three genotype polymorphism, Asn/Asn (255 bp ribbon), Asn/Ser (97 bp and 158 bp), and Ser/Ser (97 bp, 158 bp, and 255 bp). AFC has the highest predictor for ovarian response with AUC 0.922 (CI 95% 0.833-1.000). AMH also showed high predicting value (AUC 0.843 CI 95% 0.663-1.000). The multivariate analysis revealed combination of AFC, AMH, age, and basal FSH is a good model for ovarian response prediction (AUC=0.97). No significant relation between Asn/Asn, Asn/Ser, or Ser/Ser genotype FSHR polymorphism with ovarian response (p = 0.866) and total dose of rRSH (p = 0.08). This study showed that model combination of AFC, AMH, patient’s age and basal FSH are very good to predict number of mature oocytes.

Effect of human cell malignancy on activity of DNA polymerase iota.

PubMed

Kazakov, A A; Grishina, E E; Tarantul, V Z; Gening, L V

2010-07-01

An increased level of mutagenesis, partially caused by imbalanced activities of error prone DNA polymerases, is a key symptom of cell malignancy. To clarify the possible role of incorrect DNA polymerase iota (Pol iota) function in increased frequency of mutations in mammalian cells, the activity of this enzyme in extracts of cells of different mouse organs and human eye (melanoma) and eyelid (basal-cell skin carcinoma) tumor cells was studied. Both Mg2+, considered as the main activator of the enzyme reaction of in vivo DNA replication, and Mn2+, that activates homogeneous Pol iota preparations in experiments in vitro more efficiently compared to all other bivalent cations, were used as cofactors of the DNA polymerase reaction in these experiments. In the presence of Mg2+, the enzyme was active only in cell extracts of mouse testicles and brain, whereas in the presence of Mn2+ the activity of Pol iota was found in all studied normal mouse organs. It was found that in cell extracts of both types of malignant tumors (basal-cell carcinoma and melanoma) Pol iota activity was observed in the presence of either Mn2+ or Mg2+. Manganese ions activated Pol iota in both cases, though to a different extent. In the presence of Mn2+ the Pol iota activity in the basal-cell carcinoma exceeded 2.5-fold that in control cells (benign tumors from the same eyelid region). In extracts of melanoma cells in the presence of either cation, the level of the enzyme activity was approximately equal to that in extracts of cells of surrounding tumor-free tissues as well as in eyes removed after traumas. The distinctive feature of tissue malignancy (in basal-cell carcinoma and in melanoma) was the change in DNA synthesis revealed as Mn2+-activated continuation of DNA synthesis after incorrect incorporation of dG opposite dT in the template by Pol iota. Among cell extracts of different normal mouse organs, only those of testicles exhibited a similar feature. This similarity can be explained by cell division blocking that occurs in all normal cells except in testicles and in malignant cells.

The periesophageal celom of the articulate brachiopod Hemithyris psittacea (Rhynchonelliformea, Brachiopoda).

PubMed

Kuzmina, Tatyana V; Malakhov, Vladimir V

2011-02-01

The celomic system of the articulate brachiopod Hemithyris psittacea is composed of the perivisceral cavity, the canal system of the lophophore, and the periesophageal celom. We study the microscopic anatomy and ultrastructure of the periesophageal celom using scanning and transmission electron microscopy. The periesophageal celom surrounds the esophagus, is isolated from the perivisceral cavity, and is divided by septa. The lining of the periesophageal celom includes two types of cells, epithelial cells and myoepithelial cells, both are monociliary. Some epithelial cells have long processes extending along the basal lamina, suggesting that these cells might function as podocytes. The myoepithelial cells have basal myofilaments and may be overlapped by the apical processes of the adjacent epithelial cells. The periesophageal celom forms protrusions that penetrate the extracellular matrix (ECM) of the body wall above the mouth and the ECM that surrounds the esophagus. The canals of the esophageal ECM form a complicated system. The celomic lining of the external circumferential canals consists of the epithelial cells and the podocyte-like cells. The deepest canals lack a lumen; they are filled with the muscle cells surrounded by basal lamina. These branched canals might perform dual functions. First, they increase the surface area and might therefore facilitate ultrafiltration through the podocyte-like cells. Second, the deepest canals form the thickened muscle wall of the esophagus and could be necessary for antiperistalsis of the gut. Copyright © 2010 Wiley-Liss, Inc.

Picking Cell Lines for High-Throughput Transcriptomic Toxicity ...

EPA Pesticide Factsheets

High throughput, whole genome transcriptomic profiling is a promising approach to comprehensively evaluate chemicals for potential biological effects. To be useful for in vitro toxicity screening, gene expression must be quantified in a set of representative cell types that captures the diversity of potential responses across chemicals. The ideal dataset to select these cell types would consist of hundreds of cell types treated with thousands of chemicals, but does not yet exist. However, basal gene expression data may be useful as a surrogate for representing the relevant biological space necessary for cell type selection. The goal of this study was to identify a small (< 20) number of cell types that capture a large, quantifiable fraction of basal gene expression diversity. Three publicly available collections of Affymetrix U133+2.0 cellular gene expression data were used: 1) 59 cell lines from the NCI60 set; 2) 303 primary cell types from the Mabbott et al (2013) expression atlas; and 3) 1036 cell lines from the Cancer Cell Line Encyclopedia. The data were RMA normalized, log-transformed, and the probe sets mapped to HUGO gene identifiers. The results showed that <20 cell lines capture only a small fraction of the total diversity in basal gene expression when evaluated using either the entire set of 20960 HUGO genes or a subset of druggable genes likely to be chemical targets. The fraction of the total gene expression variation explained was consistent when

Basal melt beneath whillans ice stream and ice streams A and C

NASA Technical Reports Server (NTRS)

Joughin, I.; Teluezyk, S.; Engelhardt, H.

2002-01-01

We have used a recently derived map of the velocity of Whillans Ice Stream and Ice Streams A and C to help estimate basal melt. Temperature was modeled with a simple vertical advection-diffusion equation, 'tuned' to match temperature profiles. We find that most of the melt occurs beneath the tributaries where larger basal shear stresses and thicker ice favors greater melt (e.g., 10-20 mm/yr). The occurrence of basal freezing is predicted beneath much of the ice plains of Ice Stream C and Whillans Ice Stream. Modelled melt rates for when Ice Stream C was active suggest there was just enough melt water generated in its tributaries to balance basal freezing on its ice plain. Net basal melt for Whillans Ice Stream is positive due to smaller basal temperature gradients. Modelled temperatures on Whillans Ice Stream, however, were constrained by a single temperature profile at UpB. Basal temperature gradients for Whillans B1 and Ice Stream A may have conditions more similar to those beneath Ice Streams C and D, in which case, there may not be sufficient melt to sustain motion. This would be consistent with the steady deceleration of Whillans stream over the last few decades.

Apico-basal forces exerted by apoptotic cells drive epithelium folding.

PubMed

Monier, Bruno; Gettings, Melanie; Gay, Guillaume; Mangeat, Thomas; Schott, Sonia; Guarner, Ana; Suzanne, Magali

2015-02-12

Epithelium folding is a basic morphogenetic event that is essential in transforming simple two-dimensional epithelial sheets into three-dimensional structures in both vertebrates and invertebrates. Folding has been shown to rely on apical constriction. The resulting cell-shape changes depend either on adherens junction basal shift or on a redistribution of myosin II, which could be driven by mechanical signals. Yet the initial cellular mechanisms that trigger and coordinate cell remodelling remain largely unknown. Here we unravel the active role of apoptotic cells in initiating morphogenesis, thus revealing a novel mechanism of epithelium folding. We show that, in a live developing tissue, apoptotic cells exert a transient pulling force upon the apical surface of the epithelium through a highly dynamic apico-basal myosin II cable. The apoptotic cells then induce a non-autonomous increase in tissue tension together with cortical myosin II apical stabilization in the surrounding tissue, eventually resulting in epithelium folding. Together our results, supported by a theoretical biophysical three-dimensional model, identify an apoptotic myosin-II-dependent signal as the initial signal leading to cell reorganization and tissue folding. This work further reveals that, far from being passively eliminated as generally assumed (for example, during digit individualization), apoptotic cells actively influence their surroundings and trigger tissue remodelling through regulation of tissue tension.

Skeletal stem cell and bone implant interactions are enhanced by LASER titanium modification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sisti, Karin E., E-mail: karinellensisti@gmail.com; Biomaterials Group, Institute of Chemistry, São Paulo State University; Federal University of Mato Grosso do Sul

Purpose: To evaluate the osteo-regenerative potential of Titanium (Ti) modified by Light Amplification by Stimulated Emission of Radiation (LASER) beam (Yb-YAG) upon culture with human Skeletal Stem Cells (hSSCs{sup 1}). Methods: Human skeletal cell populations were isolated from the bone marrow of haematologically normal patients undergoing primary total hip replacement following appropriate consent. STRO-1{sup +} hSSC{sup 1} function was examined for 10 days across four groups using Ti discs: i) machined Ti surface group in basal media (Mb{sup 2}), ii) machined Ti surface group in osteogenic media (Mo{sup 3}), iii) LASER-modified Ti group in basal media (Lb{sup 4}) and, iv)more » LASER-modified Ti group in osteogenic media (Lo{sup 5}). Molecular analysis and qRT-PCR as well as functional analysis including biochemistry (DNA, Alkaline Phosphatase (ALP{sup 6}) specific activity), live/dead immunostaining (Cell Tracker Green (CTG{sup 7})/Ethidium Homodimer-1 (EH-1{sup 8})), and fluorescence staining (for vinculin and phalloidin) were undertaken. Inverted, confocal and Scanning Electron Microscopy (SEM) approaches were used to characterise cell adherence, proliferation, and phenotype. Results: Enhanced cell spreading and morphological rearrangement, including focal adhesions were observed following culture of hSSCs{sup 1} on LASER surfaces in both basal and osteogenic conditions. Biochemical analysis demonstrated enhanced ALP{sup 6} specific activity on the hSSCs{sup 1}-seeded on LASER-modified surface in basal culture media. Molecular analysis demonstrated enhanced ALP{sup 6} and osteopontin expression on titanium LASER treated surfaces in basal conditions. SEM, inverted microscopy and confocal laser scanning microscopy confirmed extensive proliferation and migration of human bone marrow stromal cells on all surfaces evaluated. Conclusions: LASER-modified Ti surfaces modify the behaviour of hSSCs.{sup 1} In particular, SSC{sup 1} adhesion, osteogenic gene expression, cell morphology and cytoskeleton structure were affected. The current studies show Ti LASER modification can enhance the osseointegration between Ti and skeletal cells, with important implications for orthopaedic application. - Highlights: • Bone stem cells on LASER Ti surface display enhanced cell growth and viability. • Bone stem cells on LASER Ti surface exhibit marked biocompatibility. • Human bone stem cells on LASER Ti surface exhibit altered morphology. • LASER Ti enhance osteogenic differentiation of human bone skeletal stem cells. • LASER Ti provides a unique approach to enhance osseointegration with the material.« less

Basal Cell Carcinoma: Pathogenesis, Epidemiology, Clinical Features, Diagnosis, Histopathology, and Management

PubMed Central

Marzuka, Alexander G.; Book, Samuel E.

2015-01-01

Basal cell carcinoma (BCC) is the most common malignancy. Exposure to sunlight is the most important risk factor. Most, if not all, cases of BCC demonstrate overactive Hedgehog signaling. A variety of treatment modalities exist and are selected based on recurrence risk, importance of tissue preservation, patient preference, and extent of disease. The pathogenesis, epidemiology, clinical features, diagnosis, histopathology, and management of BCC will be discussed in this review. PMID:26029015

[Gorlin-Goltz syndrome--a case report].

PubMed

Debski, Tomasz; Jethon, Józef

2010-06-01

The Gorlin-Goltz syndrome (GGS) (the nevoid basal cell carcinoma syndrome-NBCCS) is an autosomal dominant syndrome caused by mutations found on chromosome 9. The syndrome is characterized by increased predisposition to develop a basal cell carcinoma and associated with multiorgan anomalies. To present a case of GGS and explain modern standards of care for patients with this syndrome. Authors report the case of a 36-year-old patient who was admitted to the Plastic Surgery Clinic due to numerous basal cell carcinomas. Previously patient underwent an orthopaedic, neurologic, dermatologic, stomatologic and surgery treatment due to particular anomalies which characterize this syndrome. Comprehensive interview and broadening of the diagnostics enabled to diagnose GGS and to introduce the appropriate treatment. GGS is a multidisciplinary problem and widespread knowledge of this syndrome could accelerate the diagnosis process. Early diagnosis of GGS allows to introduce the secondary prophylaxis and to apply the appropriate treatment to slow the progress of the syndrome.

Multiple superficial basal cell carcinomata--topical imiquimod versus curette and cryotherapy.

PubMed

Dixon, Anthony J

2005-01-01

Superficial basal cell carcinoma can be successfully managed by means other than surgical excision. Nonexcisional approaches include topical imiquimod, and curette and cryotherapy (C&C). This article discusses the management of an insulin dependent diabetic man aged 52 years presenting with 17 torso basal cell carcinomas (BCCs); mostly superficial BCCs (SBCCs). Half were treated with topical imiquimod. The remaining lesions were treated with curette and cryotherapy. All lesions resolved with proven histologic clearance. The patient considered C&C caused him less discomfort and disruption. He developed a late secondary infection in some sites treated with imiquimod. At 12 months there was no evidence of recurrence though new nodular BCCs and SBCCs had developed elsewhere on his upper torso. He has elected to have future SBCCs managed with C&C. While excisional surgery remains the benchmark management for nonmelanoma skin cancer, topical imiquimod and C&C are important options for treating SBCCs.

Implant-retained skull prosthesis to cover a large defect of the hairy skull resulting from treatment of a basal cell carcinoma: A clinical report.

PubMed

Hoekstra, Jitske; Vissink, Arjan; Raghoebar, Gerry M; Visser, Anita

2017-05-01

Skin carcinoma, particularly basal cell carcinoma, and its treatment can result in large defects of the hairy skull. A 53-year-old man is described who was surgically treated for a large basal cell carcinoma invading the skin and underlying tissue at the top of the hairy skull. Treatment consisted of resecting the tumor and external part of the skull bone. To protect the brain and to cover the defect of the hairy skull, an acrylic resin skull prosthesis with hair was designed to mask the defect. The skull prosthesis was retained on 8 extraoral implants placed at the margins of the defect in the skull bone. The patient was satisfied with the treatment outcome. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Adenoid cystic carcinoma of breast: Recent advances

PubMed Central

Miyai, Kosuke; Schwartz, Mary R; Divatia, Mukul K; Anton, Rose C; Park, Yong Wook; Ayala, Alberto G; Ro, Jae Y

2014-01-01

Adenoid cystic carcinoma (ACC) of the breast is a rare special subtype of breast cancer characterized by the presence of a dual cell population of luminal and basaloid cells arranged in specific growth patterns. Most breast cancers with triple-negative, basal-like breast features (i.e., tumors that are devoid of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, and express basal cell markers) are generally high-grade tumors with an aggressive clinical course. Conversely, while ACCs also display a triple-negative, basal-like phenotype, they are usually low-grade and exhibit an indolent clinical behavior. Many discoveries regarding the molecular and genetic features of the ACC, including a specific chromosomal translocation t(6;9) that results in a MYB-NFIB fusion gene, have been made in recent years. This comprehensive review provides our experience with the ACC of the breast, as well as an overview of clinical, histopathological, and molecular genetic features. PMID:25516849

Dual actions of lindane ({gamma}-hexachlorocyclohexane) on calcium homeostasis and exocytosis in rat PC12 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heusinkveld, Harm J., E-mail: H.J.Heusinkveld@uu.n; Thomas, Gareth O.; Department of Environmental Science, Lancaster University, Lancaster LA1 4YQ

2010-10-01

The persistent organochlorine pesticide lindane is still abundantly found in the environment and in human and animal tissue samples. Lindane induces a wide range of adverse health effects, which are at least partially mediated via the known inhibition of GABA{sub A} and glycine receptors. Additionally, lindane has been reported to increase the basal intracellular Ca{sup 2+} concentration ([Ca{sup 2+}]{sub i}). As Ca{sup 2+} triggers many cellular processes, including cell death and vesicular neurotransmitter release (exocytosis), we investigated whether lindane affects exocytosis, Ca{sup 2+} homeostasis, production of reactive oxygen species (ROS) and cytotoxicity in neuroendocrine PC12 cells. Amperometric recordings and [Ca{supmore » 2+}]{sub i} imaging experiments with fura-2 demonstrated that lindane ({>=} 10 {mu}M) rapidly increases basal exocytosis and basal [Ca{sup 2+}]{sub i}. Additional imaging and electrophysiological recordings revealed that this increase was largely due to a lindane-induced membrane depolarization and subsequent opening of N- and P/Q-type voltage-gated Ca{sup 2+} channels (VGCC). On the other hand, lindane ({>=} 3 {mu}M) induced a concentration-dependent but non-specific inhibition of VGCCs, thereby limiting the lindane-induced increase in basal [Ca{sup 2+}]{sub i} and exocytosis. Importantly, the non-specific inhibition of VGCCs also reduced stimulation-evoked exocytosis and Ca{sup 2+} influx. Though lindane exposure concentration-dependently increased ROS production, cell viability was not affected indicating that the used concentrations were not acute cytotoxic. These combined findings indicate that lindane has two, partly counteracting effects. Lindane causes membrane depolarization, thereby increasing basal [Ca{sup 2+}]{sub i} and exocytosis. In parallel, lindane inhibits VGCCs, thereby limiting the basal effects and reducing stimulation-evoked [Ca{sup 2+}]{sub i} and exocytosis. This study further underlines the need to consider presynaptic, non-receptor-mediated effects in human risk assessment.« less

Unusual electron-dense dome associates with compound plasmodesmata in the embryo-suspensor of genus Sedum (Crassulaceae).

PubMed

Kozieradzka-Kiszkurno, Małgorzata; Bohdanowicz, Jerzy

2010-11-01

Plasmodesmata ensure the continuity of cytoplasm between plant cells and play an important part in the intercellular communication and signal transduction. During the development of the suspensor of both Sedum acre L. and Sedum hispanicum L., changes in the ultrastructure of plasmodesmata and adjoining cytoplasm are observed. Numerous simple plasmodesmata are present in the inner wall of the two-celled embryo separating the basal cell from the apical cell. From the early-globular to the torpedo stage of embryo development, the part of the wall separating the basal cell from the first layer of the chalazal suspensor cells is perforated by unusual, compound plasmodesmata. The role and the sort of transport through these plasmodesmata are discussed.

Predictive model for photodynamic therapy with gold nanoparticles as vehicle for the photosensitizer delivery

NASA Astrophysics Data System (ADS)

Salas-García, I.; Fanjul-Vélez, F.; Ortega-Quijano, N.; Arce-Diego, J. L.

2013-06-01

Photodynamic Therapy offers multiple advantages to treat nonmelanoma skin cancer compared to conventional treatment techniques such as surgery, radiotherapy or chemotherapy. Among these advantages are particularly relevant its noninvasive nature, the use of non ionizing radiation and its high selectivity. However the therapeutic efficiency of the current clinical protocol is not complete in all the patients and depends on the type of pathology. Emerging strategies to overcome its current shortcomings include the use of nanostructures that can act as carriers for conventional photosensitizers and improve the treatment selectivity and provide a controlled release of the photoactive agent. In this work, a model for photodynamic therapy combined with gold nanocarriers for a photosensitizer commonly used in dermatology is presented and applied to a basal cell carcinoma in order to predict the cytotoxic agent spatial and temporal evolution.

Magellanic penguin telomeres do not shorten with age with increased reproductive effort, investment, and basal corticosterone.

PubMed

Cerchiara, Jack A; Risques, Rosa Ana; Prunkard, Donna; Smith, Jeffrey R; Kane, Olivia J; Boersma, P Dee

2017-08-01

All species should invest in systems that enhance longevity; however, a fundamental adult life-history trade-off exists between the metabolic resources allocated to maintenance and those allocated to reproduction. Long-lived species will invest more in reproduction than in somatic maintenance as they age. We investigated this trade-off by analyzing correlations among telomere length, reproductive effort and output, and basal corticosterone in Magellanic penguins ( Spheniscus magellanicus ). Telomeres shorten with age in most species studied to date, and may affect adult survival. High basal corticosterone is indicative of stressful conditions. Corticosterone, and stress, has been linked to telomere shortening in other species. Magellanic penguins are a particularly good model organism for this question as they are an unusually long-lived species, exceeding their mass-adjusted predicted lifespan by 26%. Contrary to our hypothesis, we found adults aged 5 years to over 24 years of age had similar telomere lengths. Telomeres of adults did not shorten over a 3-year period, regardless of the age of the individual. Neither telomere length, nor the rate at which the telomeres changed over these 3 years, correlated with breeding frequency or investment. Older females also produced larger volume clutches until approximately 15 years old and larger eggs produced heavier fledglings. Furthermore, reproductive success ( chicks fledged/eggs laid ) is maintained as females aged. Basal corticosterone, however, was not correlated with telomere length in adults and suggests that low basal corticosterone may play a role in the telomere maintenance we observed. Basal corticosterone also declined during the breeding season and was positively correlated with the age of adult penguins. This higher basal corticosterone in older individuals, and consistent reproductive success, supports the prediction that Magellanic penguins invest more in reproduction as they age. Our results demonstrate that telomere maintenance may be a component of longevity even with increased reproductive effort, investment, and basal corticosterone.

The potential use of low-frequency tones to locate regions of outer hair cell loss.

PubMed

Kamerer, Aryn M; Diaz, Francisco J; Peppi, Marcello; Chertoff, Mark E

2016-12-01

Current methods used to diagnose cochlear hearing loss are limited in their ability to determine the location and extent of anatomical damage to various cochlear structures. In previous experiments, we have used the electrical potential recorded at the round window -the cochlear response (CR) -to predict the location of damage to outer hair cells in the gerbil. In a follow-up experiment, we applied 10 mM ouabain to the round window niche to reduce neural activity in order to quantify the neural contribution to the CR. We concluded that a significant proportion of the CR to a 762 Hz tone originated from phase-locking activity of basal auditory nerve fibers, which could have contaminated our conclusions regarding outer hair cell health. However, at such high concentrations, ouabain may have also affected the responses from outer hair cells, exaggerating the effect we attributed to the auditory nerve. In this study, we lowered the concentration of ouabain to 1 mM and determined the physiologic effects on outer hair cells using distortion-product otoacoustic emissions. As well as quantifying the effects of 1 mM ouabain on the auditory nerve and outer hair cells, we attempted to reduce the neural contribution to the CR by using near-infrasonic stimulus frequencies of 45 and 85 Hz, and hypothesized that these low-frequency stimuli would generate a cumulative amplitude function (CAF) that could reflect damage to hair cells in the apex more accurately than the 762 stimuli. One hour after application of 1 mM ouabain, CR amplitudes significantly increased, but remained unchanged in the presence of high-pass filtered noise conditions, suggesting that basal auditory nerve fibers have a limited contribution to the CR at such low frequencies. Published by Elsevier B.V.

Interrelated striated elements in vestibular hair cells of the rat

NASA Technical Reports Server (NTRS)

Ross, M. D.; Bourne, C.

1983-01-01

A series of interrelated striated organelles in types I and II vestibular hair cells of the rat which appear to be less developed in cochlear hair cells have been revealed by unusual fixation procedures, suggesting that contractile elements may play a role in sensory transduction in the inner ear, especially in the vestibular system. Included in the series of interrelated striated elements are the cuticular plate and its basal attachments to the hair cell margins, the connections of the strut array of the kinociliary basal body to the cuticular plate, and striated organelles associated with the plasma membrane and extending below the apical junctional complexes.

Agnus castus extracts inhibit prolactin secretion of rat pituitary cells.

PubMed

Sliutz, G; Speiser, P; Schultz, A M; Spona, J; Zeillinger, R

1993-05-01

In our studies on prolactin inhibition by plant extracts we focused on the effects of extracts of Vitex agnus castus and its preparations on rat pituitary cells under basal and stimulated conditions in primary cell culture. Both extracts from Vitex agnus castus as well as synthetic dopamine agonists (Lisuride) significantly inhibit basal as well as TRH-stimulated prolactin secretion of rat pituitary cells in vitro and as a consequence inhibition of prolactin secretion could be blocked by adding a dopamine receptor blocker. Therefore because of its dopaminergic effect Agnus castus could be considered as an efficient alternative phytotherapeutic drug in the treatment of slight hyperprolactinaemia.

A Growth and Yield Model for Thinned Stands of Yellow-Poplar

Treesearch

Bruce R. Knoebel; Harold E. Burkhart; Donald E. Beck

1986-01-01

Simultaneous growth and yield equations were developed for predicting basal area growth and cubic-foot volume growth and yield in thinned stands of yellow-poplar. A joint loss function involving both volume and basal area was used to estimate the coefficients in the system of equations. The estimates obtained were analytically compatible, invariant for projection...

NFE2-Related Transcription Factor 2 Coordinates Antioxidant Defense with Thyroglobulin Production and Iodination in the Thyroid Gland.

PubMed

Ziros, Panos G; Habeos, Ioannis G; Chartoumpekis, Dionysios V; Ntalampyra, Eleni; Somm, Emmanuel; Renaud, Cédric O; Bongiovanni, Massimo; Trougakos, Ioannis P; Yamamoto, Masayuki; Kensler, Thomas W; Santisteban, Pilar; Carrasco, Nancy; Ris-Stalpers, Carrie; Amendola, Elena; Liao, Xiao-Hui; Rossich, Luciano; Thomasz, Lisa; Juvenal, Guillermo J; Refetoff, Samuel; Sykiotis, Gerasimos P

2018-06-01

The thyroid gland has a special relationship with oxidative stress. While generation of oxidative substances is part of normal iodide metabolism during thyroid hormone synthesis, the gland must also defend itself against excessive oxidation in order to maintain normal function. Antioxidant and detoxification enzymes aid thyroid cells to maintain homeostasis by ameliorating oxidative insults, including during exposure to excess iodide, but the factors that coordinate their expression with the cellular redox status are not known. The antioxidant response system comprising the ubiquitously expressed NFE2-related transcription factor 2 (Nrf2) and its redox-sensitive cytoplasmic inhibitor Kelch-like ECH-associated protein 1 (Keap1) defends tissues against oxidative stress, thereby protecting against pathologies that relate to DNA, protein, and/or lipid oxidative damage. Thus, it was hypothesized that Nrf2 should also have important roles in maintaining thyroid homeostasis. Ubiquitous and thyroid-specific male C57BL6J Nrf2 knockout (Nrf2-KO) mice were studied. Plasma and thyroids were harvested for evaluation of thyroid function tests by radioimmunoassays and of gene and protein expression by real-time polymerase chain reaction and immunoblotting, respectively. Nrf2-KO and Keap1-KO clones of the PCCL3 rat thyroid follicular cell line were generated using CRISPR/Cas9 technology and were used for gene and protein expression studies. Software-predicted Nrf2 binding sites on the thyroglobulin enhancer were validated by site-directed in vitro mutagenesis and chromatin immunoprecipitation. The study shows that Nrf2 mediates antioxidant transcriptional responses in thyroid cells and protects the thyroid from oxidation induced by iodide overload. Surprisingly, it was also found that Nrf2 has a dramatic impact on both the basal abundance and the thyrotropin-inducible intrathyroidal abundance of thyroglobulin (Tg), the precursor protein of thyroid hormones. This effect is mediated by cell-autonomous regulation of Tg gene expression by Nrf2 via its direct binding to two evolutionarily conserved antioxidant response elements in an upstream enhancer. Yet, despite upregulating Tg levels, Nrf2 limits Tg iodination both under basal conditions and in response to excess iodide. Nrf2 exerts pleiotropic roles in the thyroid gland to couple cell stress defense mechanisms to iodide metabolism and the thyroid hormone synthesis machinery, both under basal conditions and in response to excess iodide.

Activation of the JAK-STAT Signaling Pathway after In Vitro Stimulation with IFNß in Multiple Sclerosis Patients According to the Therapeutic Response to IFNß

PubMed Central

Hurtado-Guerrero, Isaac; Pinto-Medel, Maria Jesús; Urbaneja, Patricia; Rodriguez- Bada, Jose Luis; León, Antonio; Guerrero, Miguel; Fernández, Óscar

2017-01-01

Interferon beta (IFNß) is a common treatment used for multiple sclerosis (MS) which acts through the activation of the JAK-STAT pathway. However, this therapy is not always effective and currently there are no reliable biomarkers to predict therapeutic response. We postulate that the heterogeneity in the response to IFNß therapy could be related to differential activation patterns of the JAK-STAT signaling pathway. Our aim was to evaluate the basal levels and the short term activation of this pathway after IFNß stimulation in untreated and IFNß treated patients, as well as according to therapeutic response. Therefore, cell surface levels of IFNAR subunits (IFNAR1 and IFNAR2) and the activated forms of STAT1 and STAT2 were assessed in peripheral blood mononuclear cells from MS patients by flow cytometry. Basal levels of each of the markers strongly correlated with the expression of the others in untreated patients, but many of these correlations lost significance in treated patients and after short term activation with IFNß. Patients who had undergone IFNß treatment showed higher basal levels of IFNAR1 and pSTAT1, but a reduced response to in vitro exposure to IFNß. Conversely, untreated patients, with lower basal levels, showed a greater ability of short term activation of this pathway. Monocytes from responder patients had lower IFNAR1 levels (p = 0.039) and higher IFNAR2 levels (p = 0.035) than non-responders just after IFNß stimulation. A cluster analysis showed that levels of IFNAR1, IFNAR2 and pSTAT1-2 in monocytes grouped 13 out of 19 responder patients with a similar expression pattern, showing an association of this pattern with the phenotype of good response to IFNß (p = 0.013). Our findings suggest that an activation pattern of the IFNß signaling pathway in monocytes could be associated with a clinical phenotype of good response to IFNß treatment and that a differential modulation of the IFNAR subunits in monocytes could be related with treatment effectiveness. PMID:28103257

Purification and Characterization of the Bacterial Flagellar Basal Body from Salmonella enterica.

PubMed

Aizawa, Shin-Ichi

2017-01-01

The bacterial flagellum is a motility organelle. The flagellum is composed of three main structures: the basal body as a rotary engine embedded in the cellular membranes and cell wall, the long external filament that acts as a propeller, and the hook acting as a universal joint that connects them. I describe protocols for the purification of the filament and hook-basal body from Salmonella enterica serovar Typhimurium.

Coupling between apical tension and basal adhesion allow epithelia to collectively sense and respond to substrate topography over long distances.

PubMed

Broaders, Kyle E; Cerchiari, Alec E; Gartner, Zev J

2015-12-01

Epithelial sheets fold into complex topographies that contribute to their function in vivo. Cells can sense and respond to substrate topography in their immediate vicinity by modulating their interfacial mechanics, but the extent to which these mechanical properties contribute to their ability to sense substrate topography across length scales larger than a single cell has not been explored in detail. To study the relationship between the interfacial mechanics of single cells and their collective behavior as tissues, we grew cell-sheets on substrates engraved with surface features spanning macroscopic length-scales. We found that many epithelial cell-types sense and respond to substrate topography, even when it is locally nearly planar. Cells clear or detach from regions of local negative curvature, but not from regions with positive or no curvature. We investigated this phenomenon using a finite element model where substrate topography is coupled to epithelial response through a balance of tissue contractility and adhesive forces. The model correctly predicts the focal sites of cell-clearing and epithelial detachment. Furthermore, the model predicts that local tissue response to substrate curvature is a function of the surrounding topography of the substrate across long distances. Analysis of cell-cell and cell-substrate contact angles suggests a relationship between these single-cell interfacial properties, epithelial interfacial properties, and collective epithelial response to substrate topography. Finally, we show that contact angles change upon activation of oncogenes or inhibition of cell-contractility, and that these changes correlate with collective epithelial response. Our results demonstrate that in mechanically integrated epithelial sheets, cell contractility can be transmitted through multiple cells and focused by substrate topography to affect a behavioral response at distant sites.

Low basal salivary cortisol is associated with teacher-reported symptoms of conduct disorder.

PubMed

Oosterlaan, Jaap; Geurts, Hilde M; Knol, Dirk L; Sergeant, Joseph A

2005-03-30

Cortisol has been implicated in psychobiological explanations of antisocial behavior. This study measured basal salivary cortisol in a sample of 25 children (age range 6 to 12 years) selected to vary in levels of antisocial behavior. Regression analyses were used to predict cortisol concentrations from parent- and teacher-reported symptoms. Parent-reported symptoms did not predict basal cortisol. Teacher-reported conduct disorder (CD) symptoms explained 38% of the variance in the cortisol concentrations, with high symptom severity associated with low cortisol. When a distinction was made between aggressive and non-aggressive CD symptoms, aggressive CD symptoms were more clearly related to low cortisol than non-aggressive CD symptoms. In contrast to previous research, no evidence was found for a mediating role of anxiety symptoms in the relationship between CD and cortisol. The results support biologically based models of antisocial behavior in children that involve reduced autonomic activity.

Colonization and Intrusive Invasion of Potato Psyllid by 'Candidatus Liberibacter solanacearum'.

PubMed

Cicero, Joseph M; Fisher, Tonja W; Qureshi, Jawwad A; Stansly, Philip A; Brown, Judith K

2017-01-01

Previous studies have shown that the fastidious bacterial plant pathogen 'Candidatus Liberibacter solanacearum' (CLso) is transmitted circulatively and propagatively by the potato psyllid (PoP) Bactericera cockerelli. In this study, the temporal and spatial interrelationships between CLso PoP were investigated by scanning electron microscopy of the digestive system of PoP immature and adult instars and salivary glands of adults post CLso ingestion. CLso biofilms were not detectable on the outer midgut surface of the first and second instars; however, for third to fifth instars and teneral and mature adults, biofilms were observed in increasing numbers in each successive developmental stage. In adult PoP midguts, CLso cells were observed between the basal lamina and basal epithelial cell membranes; in basal laminar perforations, on the outer basal laminar surface, and in the ventricular lumen, epithelial cytosol, and filter chamber periventricular space. CLso were also abundantly visible in the salivary gland pericellular spaces and in the epidermal cell cytosol of the head. Collectively, these results point to an intrusive, systemic invasion of PoP by CLso that employs an endo/exocytosis-like mechanism, in the context of a propagative, circulative mode of transmission.

Development of basal endosperm transfer cells in Sorghum bicolor (L.) Moench and its relationship with caryopsis growth.

PubMed

Wang, Hui-Hui; Wang, Zhong; Wang, Feng; Gu, Yun-Jie; Liu, Zhi

2012-04-01

During sorghum caryopsis development, endosperm epidermal cells near the basal main vascular bundle are specialized by depositing wall ingrowths, differentiating into basal endosperm transfer cells (BETCs). All the BETCs together compose the basal endosperm transfer layer (BETL). BETCs are the first cell type to become histologically differentiated during endosperm development. The initiation and subsequent development of BETCs shows the pattern of temporal and spatial gradient. The developmental process of BETL can be divided into four stages: initiation, differentiation, functional, and apoptosis stage. A placental sac full of nutrient solutions would emerge, enlarge, and eventually disappear between the outmost layer of BETL and nucellar cells during caryopsis development. BETCs have dense cytoplasm rich in mitochondria, lamellar rough endoplasmic reticulum, Golgi bodies, and their secretory vesicles. They show a series of typical characteristics of senescence such as nuclei distortion and subcellular organelle deterioration during their specialization. BETCs probably play an active role in nutrient transfer into the starchy endosperm and embryo. The occurrence, development, and apoptosis of BETCs are in close relation to the caryopsis growth and maturation especially the enrichment of endosperm and the growth of embryo. The timing when BETL is fully developed, composed of three to four layers in radial direction and 70 to 80 rows in tangential direction, consists with the timing when average daily gain of caryopsis dry weight reaches its maximum. It is conceivable that measures that delay the senescence and death of BETCs would help to increase the crop yield.

Comparative study of the chondrogenic potential of human bone marrow stromal cells, neonatal chondrocytes and adult chondrocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saha, Sushmita; Kirkham, Jennifer; NIHR Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Chapel Allerton Hospital, Leeds LS74SA

2010-10-22

Research highlights: {yields} This study has characterised three different cell types under conditions similar to those used for autologous chondrocyte implantation (ACI) for applications in cartilage repair/regeneration. {yields} Compared for the first time the chondrogenic potential of neonatal chondrocytes with human bone marrow stromal cells (HBMSCs) and adult chondrocytes. {yields} Demonstrated that adult chondrocytes hold greatest potential for use in ACI based on their higher proliferation rates, lower alkaline phosphatise activity and enhanced expression of chondrogenic genes. {yields} Demonstrated the need for chondroinduction as a necessary pre-requisite to efficient chondrogenesis in vitro and, by extrapolation, for cell based therapy (e.g.more » ACI or cartilage tissue engineering). -- Abstract: Cartilage tissue engineering is still a major clinical challenge with optimisation of a suitable source of cells for cartilage repair/regeneration not yet fully addressed. The aims of this study were to compare and contrast the differences in chondrogenic behaviour between human bone marrow stromal cells (HBMSCs), human neonatal and adult chondrocytes to further our understanding of chondroinduction relative to cell maturity and to identify factors that promote chondrogenesis and maintain functional homoeostasis. Cells were cultured in monolayer in either chondrogenic or basal medium, recapitulating procedures used in existing clinical procedures for cell-based therapies. Cell doubling time, morphology and alkaline phosphatase specific activity (ALPSA) were determined at different time points. Expression of chondrogenic markers (SOX9, ACAN and COL2A1) was compared via real time polymerase chain reaction. Amongst the three cell types studied, HBMSCs had the highest ALPSA in basal culture and lowest ALPSA in chondrogenic media. Neonatal chondrocytes were the most proliferative and adult chondrocytes had the lowest ALPSA in basal media. Gene expression analysis revealed a difference in the temporal expression of chondrogenic markers which were up regulated in chondrogenic medium compared to levels in basal medium. Of the three cell types studied, adult chondrocytes offer a more promising cell source for cartilage tissue engineering. This comparative study revealed differences between the microenvironment of all three cell types and provides useful information to inform cell-based therapies for cartilage regeneration.« less

Current data of targeted therapies for the treatment of triple-negative advanced breast cancer: empiricism or evidence-based?

PubMed

Petrelli, Fausto; Cabiddu, Mary; Ghilardi, Mara; Barni, Sandro

2009-10-01

Approximately 10 - 15% of breast carcinomas (BCs) are known to be 'triple-negative (TN) receptor' (i.e., not expressing ER or PR and not exhibiting overexpression and/or gene amplification of HER2-neu). Triple-negative BCs comprise approximately 85% of all basal-type tumours. Classically, basal-like BCs have been characterised by low expression of ER, PR, and HER2 neu and high expression of CK5, CK14, caveolin-1, CAIX, p63, and EGFR (HER1), which reflects the mammary gland basal/myoepithelial cell component. Although there is no standard first-line chemotherapy regimen for metastatic TN BCs, anthracycline- and taxane-containing regimens are acceptable treatments. A large number of agents, including DNA-damaging agents, EGFR inhibitors, antiangiogenic agents and novel taxane formulations are currently being tested in clinical trials for first-line and pretreated patients. Limited experiences with platinum salts, poly(ADP-ribose) polymerase (PARP) inhibitors, cetuximab, bevacizumab and ixabepilone have been published in recent years and will be reported. Novel immunohistochemistry analysis for identification of basal like/TN phenotype are awaited to correctly select this population. The clinical trials investigating new agents have to be designed for a specific (and possibly large) subset of patients with BC. In the future, a gene array platform with greater sensitivity for distinguishing the various BC subtypes, as well as having the power to predict the molecular biology of the disease, will be an indispensible tool for treatment selection. Currently, treatment of TN BC is more empirical than evidence-based. The cornerstone of treatment is chemotherapy, but in the near future, novel target agents will emerge as possible partners.

Effects and risk assessment of linear alkylbenzene sulfonates in agricultural soil. 1. Short-term effects on soil microbiology.

PubMed

Elsgaard, L; Petersen, S O; Debosz, K

2001-08-01

Linear alkylbenzene sulfonates (LAS) may occur in sewage sludge that is applied to agricultural soil, in which LAS can be inhibitory to biological activity. As a part of a broader risk assessment of LAS in the terrestrial environment, we tested the short-term effects of aqueous LAS on microbial parameters in a sandy agricultural soil that was incubated for up to 11 d. The assays included 10 microbial soil parameters; ethylene degradation; potential ammonium oxidation; potential dehydrogenase activity; beta-glucosidase activity; iron reduction; the populations of cellulolytic bacteria, fungi and actinomycetes; the basal soil respiration; and the phospholipid fatty acid (PLFA) content. Except for beta-glucosidase activity, basal respiration, and total PLFA content, all soil parameters were sensitive to LAS, with EC10 values in the range of less than 8 to 22 mg/kg dry weight. This probably reflected a similar mode of LAS toxicity, ascribed to cell membrane interactions, and showed that sensitivity to LAS was common for various soil microorganisms. The extracellular beta-glucosidase activity was rather insensitive to LAS (ECI10, 47 mg/kg dry wt), whereas the basal soil respiration was not inhibited even at 793 mg/kg dry weight. This was interpreted as a combined response of inhibited and stimulated compartments of the microbial community. The PLFA content, surprisingly, showed no decrease even at 488 mg/kg. In conclusion, LAS inhibited specific microbial activities, although this could not be deduced from the basal respiration or the total PLFA content. The lowest EC10 values for microbial soil parameters were slightly higher than the predicted no-effect concentrations recently derived for plants and soil fauna (approximately 5 mg/kg dry wt).

The structural phase diagram and oxygen equilibrium partial pressure of YBa 2Cu 3O 6+ x studied by neutron powder diffraction and gas volumetry

NASA Astrophysics Data System (ADS)

Andersen, N. H.; Lebech, B.; Poulsen, H. F.

1990-12-01

An experimental technique based on neutron powder diffraction and gas volumetry is presented and used to study the structural phase diagram of YBa 2Cu 3O 6+ x under equilibrium conditions in an extended part of ( x, T)-phase (0.15< x<0.92 and 25° C< T<725°C). Our experimental observations lend strong support to a recent two-dimensional anisotropic next-nearest-neighbour Ising model calculation (the ASYNNNI model) of the basal plane oxygen ordering based of first principle interaction parameters. Simultaneous measurements of the oxygen equilibrium partial pressure show anomalies, one of which proves the thermodynamic stability of the orthorhombic OII double cell structure. Striking similarity with predictions of recent model calculations support that another anomaly may be interpreted to result from local one-dimensional fluctuations in the distribution of oxygen atoms in the basal plane of tetragonal YBCO. Our pressure data also indicate that x=0.92 is a maximum obtainable oxygen concentration for oxygen pressures below 760 Torr.

Basal Ganglia Neuromodulation Over Multiple Temporal and Structural Scales—Simulations of Direct Pathway MSNs Investigate the Fast Onset of Dopaminergic Effects and Predict the Role of Kv4.2

PubMed Central

Lindroos, Robert; Dorst, Matthijs C.; Du, Kai; Filipović, Marko; Keller, Daniel; Ketzef, Maya; Kozlov, Alexander K.; Kumar, Arvind; Lindahl, Mikael; Nair, Anu G.; Pérez-Fernández, Juan; Grillner, Sten; Silberberg, Gilad; Hellgren Kotaleski, Jeanette

2018-01-01

The basal ganglia are involved in the motivational and habitual control of motor and cognitive behaviors. Striatum, the largest basal ganglia input stage, integrates cortical and thalamic inputs in functionally segregated cortico-basal ganglia-thalamic loops, and in addition the basal ganglia output nuclei control targets in the brainstem. Striatal function depends on the balance between the direct pathway medium spiny neurons (D1-MSNs) that express D1 dopamine receptors and the indirect pathway MSNs that express D2 dopamine receptors. The striatal microstructure is also divided into striosomes and matrix compartments, based on the differential expression of several proteins. Dopaminergic afferents from the midbrain and local cholinergic interneurons play crucial roles for basal ganglia function, and striatal signaling via the striosomes in turn regulates the midbrain dopaminergic system directly and via the lateral habenula. Consequently, abnormal functions of the basal ganglia neuromodulatory system underlie many neurological and psychiatric disorders. Neuromodulation acts on multiple structural levels, ranging from the subcellular level to behavior, both in health and disease. For example, neuromodulation affects membrane excitability and controls synaptic plasticity and thus learning in the basal ganglia. However, it is not clear on what time scales these different effects are implemented. Phosphorylation of ion channels and the resulting membrane effects are typically studied over minutes while it has been shown that neuromodulation can affect behavior within a few hundred milliseconds. So how do these seemingly contradictory effects fit together? Here we first briefly review neuromodulation of the basal ganglia, with a focus on dopamine. We furthermore use biophysically detailed multi-compartmental models to integrate experimental data regarding dopaminergic effects on individual membrane conductances with the aim to explain the resulting cellular level dopaminergic effects. In particular we predict dopaminergic effects on Kv4.2 in D1-MSNs. Finally, we also explore dynamical aspects of the onset of neuromodulation effects in multi-scale computational models combining biochemical signaling cascades and multi-compartmental neuron models. PMID:29467627

Use of the DISST Model to Estimate the HOMA and Matsuda Indexes Using Only a Basal Insulin Assay

PubMed Central

Docherty, Paul D.; Chase, J. Geoffrey

2014-01-01

Background: It is hypothesized that early detection of reduced insulin sensitivity (SI) could prompt intervention that may reduce the considerable financial strain type 2 diabetes mellitus (T2DM) places on global health care. Reduction of the cost of already inexpensive SI metrics such as the Matsuda and HOMA indexes would enable more widespread, economically feasible use of these metrics for screening. The goal of this research was to determine a means of reducing the number of insulin samples and therefore the cost required to provide an accurate Matsuda Index value. Method: The Dynamic Insulin Sensitivity and Secretion Test (DISST) model was used with the glucose and basal insulin measurements from an Oral Glucose Tolerance Test (OGTT) to predict patient insulin responses. The insulin response to the OGTT was determined via population based regression analysis that incorporated the 60-minute glucose and basal insulin values. Results: The proposed method derived accurate and precise Matsuda Indices as compared to the fully sampled Matsuda (R = .95) using only the basal assay insulin-level data and 4 glucose measurements. Using a model employing the basal insulin also allows for determination of the 1-day HOMA value. Conclusion: The DISST model was successfully modified to allow for the accurate prediction an individual’s insulin response to the OGTT. In turn, this enabled highly accurate and precise estimation of a Matsuda Index using only the glucose and basal insulin assays. As insulin assays account for the majority of the cost of the Matsuda Index, this model offers a significant reduction in assay cost. PMID:24876431

Basal and dynamic relationships between implicit power motivation and estradiol in women.

PubMed

Stanton, Steven J; Schultheiss, Oliver C

2007-12-01

This study investigated basal and reciprocal relationships between implicit power motivation (n Power), a preference for having impact and dominance over others, and both salivary estradiol and testosterone in women. 49 participants completed the Picture Story Exercise, a measure of n Power. During a laboratory contest, participants competed in pairs on a cognitive task and contest outcome (win vs. loss) was experimentally varied. Estradiol and testosterone levels were determined in saliva samples collected at baseline and several times post-contest, including 1 day post-contest. n Power was positively associated with basal estradiol concentrations. The positive correlation between n Power and basal estradiol was stronger in single women, women not taking oral contraceptives, or in women with low-CV estradiol samples than in the overall sample of women. Women's estradiol responses to a dominance contest were influenced by the interaction of n Power and contest outcome: estradiol increased in power-motivated winners but decreased in power-motivated losers. For power-motivated winners, elevated levels of estradiol were still present the day after the contest. Lastly, n Power and estradiol did not correlate with self-reported dominance and correlated negatively with self-reported aggression. Self-reported dominance and aggression did not predict estradiol changes as a function of contest outcome. Overall, n Power did not predict basal testosterone levels or testosterone changes as a function of dominance contest outcome.

Metabolic biomarkers for response to PI3K inhibition in basal-like breast cancer

PubMed Central

2013-01-01

Introduction The phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in cancer cells through numerous mutations and epigenetic changes. The recent development of inhibitors targeting different components of the PI3K pathway may represent a valuable treatment alternative. However, predicting efficacy of these drugs is challenging, and methods for therapy monitoring are needed. Basal-like breast cancer (BLBC) is an aggressive breast cancer subtype, frequently associated with PI3K pathway activation. The objectives of this study were to quantify the PI3K pathway activity in tissue sections from xenografts representing basal-like and luminal-like breast cancer before and immediately after treatment with PI3K inhibitors, and to identify metabolic biomarkers for treatment response. Methods Tumor-bearing animals (n = 8 per treatment group) received MK-2206 (120 mg/kg/day) or BEZ235 (50 mg/kg/day) for 3 days. Activity in the PI3K/Akt/mammalian target of rapamycin pathway in xenografts and human biopsies was evaluated using a novel method for semiquantitative assessment of Aktser473 phosphorylation. Metabolic changes were assessed by ex vivo high-resolution magic angle spinning magnetic resonance spectroscopy. Results Using a novel dual near-infrared immunofluorescent imaging method, basal-like xenografts had a 4.5-fold higher baseline level of pAktser473 than luminal-like xenografts. Following treatment, basal-like xenografts demonstrated reduced levels of pAktser473 and decreased proliferation. This correlated with metabolic changes, as both MK-2206 and BEZ235 reduced lactate concentration and increased phosphocholine concentration in the basal-like tumors. BEZ235 also caused increased glucose and glycerophosphocholine concentrations. No response to treatment or change in metabolic profile was seen in luminal-like xenografts. Analyzing tumor sections from five patients with BLBC demonstrated that two of these patients had an elevated pAktser473 level. Conclusion The activity of the PI3K pathway can be determined in tissue sections by quantitative imaging using an antibody towards pAktser473. Long-term treatment with MK-2206 or BEZ235 resulted in significant growth inhibition in basal-like, but not luminal-like, xenografts. This indicates that PI3K inhibitors may have selective efficacy in basal-like breast cancer with increased PI3K signaling, and identifies lactate, phosphocholine and glycerophosphocholine as potential metabolic biomarkers for early therapy monitoring. In human biopsies, variable pAktser473 levels were observed, suggesting heterogeneous PI3K signaling activity in BLBC. PMID:23448424

Asymmetric stem-cell divisions define the architecture of human oesophageal epithelium.

PubMed

Seery, J P; Watt, F M

2000-11-16

In spite of its clinical importance, little is known about the stem-cell compartment of the human oesophageal epithelium [1,2]. The epithelial basal layer consists of two distinct zones, one overlying the papillae of the supporting connective tissue (PBL) and the other covering the interpapillary zone (IBL) [3]. In examining the oesophageal basal layer, we found that proliferating cells were rare in the IBL and a high proportion of mitoses were asymmetrical, giving rise to one basal daughter and one suprabasal, differentiating daughter. In the PBL, mitoses were more frequent and predominantly symmetrical. The IBL was characterised by low expression of ?1 integrins and high expression of the beta2 laminin chain. By combining fluorescence-activated cell sorting (FACS) with in vitro clonal analysis, we obtained evidence that the IBL is enriched for stem cells. A normal oesophageal epithelium with asymmetric divisions was reconstituted on denuded oesophageal connective tissue. In contrast, asymmetric divisions were not sustained on skin connective tissue, and the epithelium formed resembled epidermis. We propose that stem cells located in the IBL give rise to differentiating daughters through asymmetric divisions in response to cues from the underlying basement membrane. Until now, stem-cell fate in stratified squamous epithelia was believed to be achieved largely through populational asymmetry [4-6].

Primary cilia maintain corneal epithelial homeostasis by regulation of the Notch signaling pathway

PubMed Central

Grisanti, Laura; Revenkova, Ekaterina; Gordon, Ronald E.

2016-01-01

Primary cilia have been linked to signaling pathways involved in cell proliferation, cell motility and cell polarity. Defects in ciliary function result in developmental abnormalities and multiple ciliopathies. Patients affected by severe ciliopathies, such as Meckel syndrome, present several ocular surface disease conditions of unclear pathogenesis. Here, we show that primary cilia are predominantly present on basal cells of the mouse corneal epithelium (CE) throughout development and in the adult. Conditional ablation of cilia in the CE leads to an increase in proliferation and vertical migration of basal corneal epithelial cells (CECs). A consequent increase in cell density of suprabasal layers results in a thicker than normal CE. Surprisingly, in cilia-deficient CE, cilia-mediated signaling pathways, including Hh and Wnt pathways, were not affected but the intensity of Notch signaling was severely diminished. Although Notch1 and Notch2 receptors were expressed normally, nuclear Notch1 intracellular domain (N1ICD) expression was severely reduced. Postnatal development analysis revealed that in cilia-deficient CECs downregulation of the Notch pathway precedes cell proliferation defects. Thus, we have uncovered a function of the primary cilium in maintaining homeostasis of the CE by balancing proliferation and vertical migration of basal CECs through modulation of Notch signaling. PMID:27122169

Individual differences in brainstem and basal ganglia structure predict postural control and balance loss in young and older adults.

PubMed

Boisgontier, Matthieu P; Cheval, Boris; Chalavi, Sima; van Ruitenbeek, Peter; Leunissen, Inge; Levin, Oron; Nieuwboer, Alice; Swinnen, Stephan P

2017-02-01

It remains unclear which specific brain regions are the most critical for human postural control and balance, and whether they mediate the effect of age. Here, associations between postural performance and corticosubcortical brain regions were examined in young and older adults using multiple structural imaging and linear mixed models. Results showed that of the regions involved in posture, the brainstem was the strongest predictor of postural control and balance: lower brainstem volume predicted larger center of pressure deviation and higher odds of balance loss. Analyses of white and gray matter in the brainstem showed that the pedunculopontine nucleus area appeared to be critical for postural control in both young and older adults. In addition, the brainstem mediated the effect of age on postural control, underscoring the brainstem's fundamental role in aging. Conversely, lower basal ganglia volume predicted better postural performance, suggesting an association between greater neural resources in the basal ganglia and greater movement vigor, resulting in exaggerated postural adjustments. Finally, results showed that practice, shorter height and heavier weight (i.e., higher body mass index), higher total physical activity, and larger ankle active (but not passive) range of motion were predictive of more stable posture, irrespective of age. Copyright © 2016 Elsevier Inc. All rights reserved.

The Tumor Suppressor Actions of the Vitamin D Receptor in Skin

DTIC Science & Technology

2013-08-01

S. Yu, et al., Basal cell carcinomas inmiceoverexpressing Gli2 in skin, Nature Genetics 24 (3) (2000) 216–217. 61] M. Nilsson, A.B. Unden, D. Krause ...Meineke V, Gartner BC, Wolfgang T, Holick MF, Reichrath J. Analysis of the vitamin D system in cutaneous malignancies. Recent Results Cancer Res...10700170] 63. Nilsson M, Unden AB, Krause D, Malmqwist U, Raza K, Zaphiropoulos PG, Toftgard R. Induction of basal cell carcinomas and trichoepitheliomas

Multiple odontogenic keratocysts associated with Gorlin-Goltz syndrome.

PubMed

Dixit, S; Acharya, S; Dixit, P B

2009-01-01

Gorlin-Goltz syndrome or Nevoid basal cell carcinoma syndrome is an autosomal dominant disorder with a predisposition to cancer. Features like basal cell carcinoma, odontogenic keratocysts, calcification of falx cerebri, bifid ribs, pits on palms and soles and hypertelorism are evident. A case of this rare disease seen on a 13 year old female patient is presented here, where multiple odontogenic keratocysts were causing disfigurement of the lower jaw as well as displacement and malocclusion of the lower teeth.

The Centrioles, Centrosomes, Basal Bodies, and Cilia of Drosophila melanogaster.

PubMed

Lattao, Ramona; Kovács, Levente; Glover, David M

2017-05-01

Centrioles play a key role in the development of the fly. They are needed for the correct formation of centrosomes, the organelles at the poles of the spindle that can persist as microtubule organizing centers (MTOCs) into interphase. The ability to nucleate cytoplasmic microtubules (MTs) is a property of the surrounding pericentriolar material (PCM). The centriole has a dual life, existing not only as the core of the centrosome but also as the basal body, the structure that templates the formation of cilia and flagellae. Thus the structure and functions of the centriole, the centrosome, and the basal body have an impact upon many aspects of development and physiology that can readily be modeled in Drosophila Centrosomes are essential to give organization to the rapidly increasing numbers of nuclei in the syncytial embryo and for the spatially precise execution of cell division in numerous tissues, particularly during male meiosis. Although mitotic cell cycles can take place in the absence of centrosomes, this is an error-prone process that opens up the fly to developmental defects and the potential of tumor formation. Here, we review the structure and functions of the centriole, the centrosome, and the basal body in different tissues and cultured cells of Drosophila melanogaster , highlighting their contributions to different aspects of development and cell division. Copyright © 2017 Lattao et al.

Abundant Occurrence of Basal Radial Glia in the Subventricular Zone of Embryonic Neocortex of a Lissencephalic Primate, the Common Marmoset Callithrix jacchus

PubMed Central

Kelava, Iva; Reillo, Isabel; Murayama, Ayako Y.; Kalinka, Alex T.; Stenzel, Denise; Tomancak, Pavel; Matsuzaki, Fumio; Lebrand, Cécile; Sasaki, Erika; Schwamborn, Jens C.; Okano, Hideyuki; Borrell, Víctor

2012-01-01

Subventricular zone (SVZ) progenitors are a hallmark of the developing neocortex. Recent studies described a novel type of SVZ progenitor that retains a basal process at mitosis, sustains expression of radial glial markers, and is capable of self-renewal. These progenitors, referred to here as basal radial glia (bRG), occur at high relative abundance in the SVZ of gyrencephalic primates (human) and nonprimates (ferret) but not lissencephalic rodents (mouse). Here, we analyzed the occurrence of bRG cells in the embryonic neocortex of the common marmoset Callithrix jacchus, a near-lissencephalic primate. bRG cells, expressing Pax6, Sox2 (but not Tbr2), glutamate aspartate transporter, and glial fibrillary acidic protein and retaining a basal process at mitosis, occur at similar relative abundance in the marmoset SVZ as in human and ferret. The proportion of progenitors in M-phase was lower in embryonic marmoset than developing ferret neocortex, raising the possibility of a longer cell cycle. Fitting the gyrification indices of 26 anthropoid species to an evolutionary model suggested that the marmoset evolved from a gyrencephalic ancestor. Our results suggest that a high relative abundance of bRG cells may be necessary, but is not sufficient, for gyrencephaly and that the marmoset's lissencephaly evolved secondarily by changing progenitor parameters other than progenitor type. PMID:22114084

Defining the cellular precursors to human breast cancer

PubMed Central

Keller, Patricia J.; Arendt, Lisa M.; Skibinski, Adam; Logvinenko, Tanya; Klebba, Ina; Dong, Shumin; Smith, Avi E.; Prat, Aleix; Perou, Charles M.; Gilmore, Hannah; Schnitt, Stuart; Naber, Stephen P.; Garlick, Jonathan A.; Kuperwasser, Charlotte

2012-01-01

Human breast cancers are broadly classified based on their gene-expression profiles into luminal- and basal-type tumors. These two major tumor subtypes express markers corresponding to the major differentiation states of epithelial cells in the breast: luminal (EpCAM+) and basal/myoepithelial (CD10+). However, there are also rare types of breast cancers, such as metaplastic carcinomas, where tumor cells exhibit features of alternate cell types that no longer resemble breast epithelium. Until now, it has been difficult to identify the cell type(s) in the human breast that gives rise to these various forms of breast cancer. Here we report that transformation of EpCAM+ epithelial cells results in the formation of common forms of human breast cancer, including estrogen receptor-positive and estrogen receptor-negative tumors with luminal and basal-like characteristics, respectively, whereas transformation of CD10+ cells results in the development of rare metaplastic tumors reminiscent of the claudin-low subtype. We also demonstrate the existence of CD10+ breast cells with metaplastic traits that can give rise to skin and epidermal tissues. Furthermore, we show that the development of metaplastic breast cancer is attributable, in part, to the transformation of these metaplastic breast epithelial cells. These findings identify normal cellular precursors to human breast cancers and reveal the existence of a population of cells with epidermal progenitor activity within adult human breast tissues. PMID:21940501

Notch signaling is significantly suppressed in basal cell carcinomas and activation induces basal cell carcinoma cell apoptosis.

PubMed

Shi, Feng-Tao; Yu, Mei; Zloty, David; Bell, Robert H; Wang, Eddy; Akhoundsadegh, Noushin; Leung, Gigi; Haegert, Anne; Carr, Nicholas; Shapiro, Jerry; McElwee, Kevin J

2017-04-01

A subset of basal cell carcinomas (BCCs) are directly derived from hair follicles (HFs). In some respects, HFs can be defined as 'ordered' skin appendage growths, while BCCs can be regarded as 'disordered' skin appendage growths. The aim of the present study was to examine HFs and BCCs to define the expression of common and unique signaling pathways in each skin appendage. Human nodular BCCs, along with HFs and non‑follicular skin epithelium from normal individuals, were examined using microarrays, qPCR, and immunohistochemistry. Subsequently, BCC cells and root sheath keratinocyte cells from HFs were cultured and treated with Notch signaling peptide Jagged1 (JAG1). Gene expression, protein levels, and cell apoptosis susceptibility were assessed using qPCR, immunoblotting, and flow cytometry, respectively. Specific molecular mechanisms were found to be involved in the process of cell self‑renewal in the HFs and BCCs, including Notch and Hedgehog signaling pathways. However, several key Notch signaling factors showed significant differential expression in BCCs compared with HFs. Stimulating Notch signaling with JAG1 induced apoptosis of BCC cells by increasing Fas ligand expression and downstream caspase-8 activation. The present study showed that Notch signaling pathway activity is suppressed in BCCs, and is highly expressed in HFs. Elements of the Notch pathway could, therefore, represent targets for the treatment of BCCs and potentially in hair follicle engineering.

Coordination of Septate Junctions Assembly and Completion of Cytokinesis in Proliferative Epithelial Tissues.

PubMed

Daniel, Emeline; Daudé, Marion; Kolotuev, Irina; Charish, Kristi; Auld, Vanessa; Le Borgne, Roland

2018-05-07

How permeability barrier function is maintained when epithelial cells divide is largely unknown. Here, we have investigated how the bicellular septate junctions (BSJs) and tricellular septate junctions (TSJs) are remodeled throughout completion of cytokinesis in Drosophila epithelia. We report that, following cytokinetic ring constriction, the midbody assembles, matures within SJs, and is displaced basally in two phases. In a first slow phase, the neighboring cells remain connected to the dividing cells by means of SJ-containing membrane protrusions pointing to the maturing midbody. Fluorescence recovery after photobleaching (FRAP) experiments revealed that SJs within the membrane protrusions correspond to the old SJs that were present prior to cytokinesis. In contrast, new SJs are assembled below the adherens junctions and spread basally to build a new belt of SJs in a manner analogous to a conveyor belt. Loss of function of a core BSJ component, the Na+/K+-ATPase pump Nervana 2 subunit, revealed that the apical-to-basal spread of BSJs drives the basal displacement of the midbody. In contrast, loss of the TSJ protein Bark beetle indicated that remodeling of TSJs is rate limiting and slowed down midbody migration. In the second phase, once the belt of SJs is assembled, the basal displacement of the midbody is accelerated and ultimately leads to abscission. This last step is temporally uncoupled from the remodeling of SJs. We propose that cytokinesis in epithelia involves the coordinated polarized assembly and remodeling of SJs both in the dividing cell and its neighbors to ensure the maintenance of permeability barrier integrity in proliferative epithelia. Copyright © 2018 Elsevier Ltd. All rights reserved.

Immunolocalization and Changes of Hydroxyproline-Rich Glycoproteins During Symbiotic Germination of Dendrobium officinale.

PubMed

Li, Yuan-Yuan; Chen, Xiao-Mei; Zhang, Ying; Cho, Yu-Hsiu; Wang, Ai-Rong; Yeung, Edward C; Zeng, Xu; Guo, Shun-Xing; Lee, Yung-I

2018-01-01

Hydroxyproline-rich glycoproteins (HRGPs) are abundant cell wall components involved in mycorrhizal symbiosis, but little is known about their function in orchid mycorrhizal association. To gain further insight into the role of HRGPs in orchid symbiosis, the location and function of HRGPs were investigated during symbiotic germination of Dendrobium officinale . The presence of JIM11 epitope in developing protocorms was determined using immunodot blots and immunohistochemical staining procedures. Real-time PCR was also employed to verify the expression patterns of genes coding for extensin-like genes selected from the transcriptomic database. The importance of HRGPs in symbiotic germination was further investigated using 3,4-dehydro-L-proline (3,4-DHP), an inhibitor of HRGP biosynthesis. In symbiotic cultures, immunodot blots of JIM11 signals were moderate in mature seeds, and the signals became stronger in swollen embryos. After germination, signal intensities decreased in developing protocorms. In contrast, in asymbiotic cultures, JIM11 signals were much lower as compared with those stages in symbiotic cultures. Immunofluorescence staining enabled the visualization of JIM11 epitope in mature embryo and protocorm cells. Positive signals were initially localized in the larger cells near the basal (suspensor) end of uninfected embryos, marking the future colonization site of fungal hyphae. After 1 week of inoculation, the basal end of embryos had been colonized, and a strong signal was detected mostly at the mid- and basal regions of the enlarging protocorm. As protocorm development progressed, the signal was concentrated in the colonized cells at the basal end. In colonized cells, signals were present in the walls and intracellularly associated with hyphae and the pelotons. The precise localization of JIM11 epitope is further examined by immunogold labeling. In the colonized cells, gold particles were found mainly in the cell wall and the interfacial matrix near the fungal cell wall. Four extensin-like genes were verified to be highly up-regulated in symbiotically germinated protocorms as compared to asymbiotically germinated ones. The 3,4-DHP treatment inhibited the accumulation of HRGPs and symbiotic seed germination. In these protocorms, fungal hyphae could be found throughout the protocorms. Our results indicate that HRGPs play an important role in symbiotic germination. They can serve as markers for fungal colonization, establishing a symbiotic compartment and constraining fungal colonization inside the basal cells of protocorms.

Immunolocalization and Changes of Hydroxyproline-Rich Glycoproteins During Symbiotic Germination of Dendrobium officinale

PubMed Central

Li, Yuan-Yuan; Chen, Xiao-Mei; Zhang, Ying; Cho, Yu-Hsiu; Wang, Ai-Rong; Yeung, Edward C.; Zeng, Xu; Guo, Shun-Xing; Lee, Yung-I

2018-01-01

Hydroxyproline-rich glycoproteins (HRGPs) are abundant cell wall components involved in mycorrhizal symbiosis, but little is known about their function in orchid mycorrhizal association. To gain further insight into the role of HRGPs in orchid symbiosis, the location and function of HRGPs were investigated during symbiotic germination of Dendrobium officinale. The presence of JIM11 epitope in developing protocorms was determined using immunodot blots and immunohistochemical staining procedures. Real-time PCR was also employed to verify the expression patterns of genes coding for extensin-like genes selected from the transcriptomic database. The importance of HRGPs in symbiotic germination was further investigated using 3,4-dehydro-L-proline (3,4-DHP), an inhibitor of HRGP biosynthesis. In symbiotic cultures, immunodot blots of JIM11 signals were moderate in mature seeds, and the signals became stronger in swollen embryos. After germination, signal intensities decreased in developing protocorms. In contrast, in asymbiotic cultures, JIM11 signals were much lower as compared with those stages in symbiotic cultures. Immunofluorescence staining enabled the visualization of JIM11 epitope in mature embryo and protocorm cells. Positive signals were initially localized in the larger cells near the basal (suspensor) end of uninfected embryos, marking the future colonization site of fungal hyphae. After 1 week of inoculation, the basal end of embryos had been colonized, and a strong signal was detected mostly at the mid- and basal regions of the enlarging protocorm. As protocorm development progressed, the signal was concentrated in the colonized cells at the basal end. In colonized cells, signals were present in the walls and intracellularly associated with hyphae and the pelotons. The precise localization of JIM11 epitope is further examined by immunogold labeling. In the colonized cells, gold particles were found mainly in the cell wall and the interfacial matrix near the fungal cell wall. Four extensin-like genes were verified to be highly up-regulated in symbiotically germinated protocorms as compared to asymbiotically germinated ones. The 3,4-DHP treatment inhibited the accumulation of HRGPs and symbiotic seed germination. In these protocorms, fungal hyphae could be found throughout the protocorms. Our results indicate that HRGPs play an important role in symbiotic germination. They can serve as markers for fungal colonization, establishing a symbiotic compartment and constraining fungal colonization inside the basal cells of protocorms. PMID:29922306

ROCK inhibition abolishes the establishment of the aquiferous system in Ephydatia muelleri (Porifera, Demospongiae).

PubMed

Schenkelaars, Quentin; Quintero, Omar; Hall, Chelsea; Fierro-Constain, Laura; Renard, Emmanuelle; Borchiellini, Carole; Hill, April L

2016-04-15

The Rho associated coiled-coil protein kinase (ROCK) plays crucial roles in development across bilaterian animals. The fact that the Rho/Rock pathway is required to initiate epithelial morphogenesis and thus to establish body plans in bilaterians makes this conserved signaling pathway key for studying the molecular mechanisms that may control early development of basally branching metazoans. The purpose of this study was to evaluate whether or not the main components of this signaling pathway exist in sponges, and if present, to investigate the possible role of the regulatory network in an early branching non-bilaterian species by evaluating ROCK function during Ephydatia muelleri development. Molecular phylogenetic analyses and protein domain predictions revealed the existence of Rho/Rock components in all studied poriferan lineages. Binding assays revealed that both Y-27632 and GSK429286A are capable of inhibiting Em-ROCK activity in vitro. Treatment with both drugs leads to impairment of growth and formation of the basal pinacoderm layer in the developing sponge. Furthermore, inhibition of Em-Rock prevents the establishment of a functional aquiferous system, including the absence of an osculum. In contrast, no effect of ROCK inhibition was observed in juvenile sponges that already possess a fully developed and functional aquiferous system. Thus, the Rho/Rock pathway appears to be essential for the proper development of the freshwater sponge, and may play a role in various cell behaviors (e.g. cell proliferation, cell adhesion and cell motility). Taken together, these data are consistent with an ancestral function of Rho/Rock signaling in playing roles in early developmental processes and may provide a new framework to study the interaction between Wnt signaling and the Rho/Rock pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterizing the efficacy of cancer therapeutics in patient-derived xenograft models of metastatic breast cancer.

PubMed

Turner, Tia H; Alzubi, Mohammad A; Sohal, Sahib S; Olex, Amy L; Dozmorov, Mikhail G; Harrell, J Chuck

2018-03-12

Basal-like breast cancers are aggressive and often metastasize to vital organs. Treatment is largely limited to chemotherapy. This study aims to characterize the efficacy of cancer therapeutics in vitro and in vivo within the primary tumor and metastatic setting, using patient-derived xenograft (PDX) models. We employed two basal-like, triple-negative PDX models, WHIM2 and WHIM30. PDX cells, obtained from mammary tumors grown in mice, were treated with twelve cancer therapeutics to evaluate their cytotoxicity in vitro. Four of the effective drugs-carboplatin, cyclophosphamide, bortezomib, and dacarbazine-were tested in vivo for their efficacy in treating mammary tumors, and metastases generated by intracardiac injection of tumor cells. RNA sequencing showed that global gene expression of PDX cells grown in the mammary gland was similar to those tested in culture. In vitro, carboplatin was cytotoxic to WHIM30 but not WHIM2, whereas bortezomib, dacarbazine, and cyclophosphamide were cytotoxic to both lines. Yet, these drugs were ineffective in treating both primary and metastatic WHIM2 tumors in vivo. Carboplatin and cyclophosphamide were effective in treating WHIM30 mammary tumors and reducing metastatic burden in the brain, liver, and lungs. WHIM2 and WHIM30 metastases showed distinct patterns of cytokeratin and vimentin expression, regardless of treatment, suggesting that different tumor cell subpopulations may preferentially seed in different organs. This study highlights the utility of PDX models for studying the efficacy of therapeutics in reducing metastatic burden in specific organs. The differential treatment responses between two PDX models of the same intrinsic subtype, in both the primary and metastatic setting, recapitulates the challenges faced in treating cancer patients and highlights the need for combination therapies and predictive biomarkers.

In Vitro Analysis of Breast Cancer Cell Line Tumourspheres and Primary Human Breast Epithelia Mammospheres Demonstrates Inter- and Intrasphere Heterogeneity

PubMed Central

Vargas, Ana Cristina; Keith, Patricia; Reid, Lynne; Wockner, Leesa; Amiri, Marjan Askarian; Sarkar, Debina; Simpson, Peter T.; Clarke, Catherine; Schmidt, Chris W.; Reynolds, Brent A.

2013-01-01

Mammosphere and breast tumoursphere culture have gained popularity as in vitro assays for propagating and analysing normal and cancer stem cells. Whether the spheres derived from different sources or parent cultures themselves are indeed single entities enriched in stem/progenitor cells compared to other culture formats has not been fully determined. We surveyed sphere-forming capacity across 26 breast cell lines, immunophenotyped spheres from six luminal- and basal-like lines by immunohistochemistry and flow cytometry and compared clonogenicity between sphere, adherent and matrigel culture formats using in vitro functional assays. Analyses revealed morphological and molecular intra- and inter-sphere heterogeneity, consistent with adherent parental cell line phenotypes. Flow cytometry showed sphere culture does not universally enrich for markers previously associated with stem cell phenotypes, although we found some cell-line specific changes between sphere and adherent formats. Sphere-forming efficiency was significantly lower than adherent or matrigel clonogenicity and constant over serial passage. Surprisingly, self-renewal capacity of sphere-derived cells was similar/lower than other culture formats. We observed significant correlation between long-term-proliferating-cell symmetric division rates in sphere and adherent cultures, suggesting functional overlap between the compartments sustaining them. Experiments with normal primary human mammary epithelia, including sorted luminal (MUC1+) and basal/myoepithelial (CD10+) cells revealed distinct luminal-like, basal-like and mesenchymal entities amongst primary mammospheres. Morphological and colony-forming-cell assay data suggested mammosphere culture may enrich for a luminal progenitor phenotype, or induce reversion/relaxation of the basal/mesenchymal in vitro selection occurring with adherent culture. Overall, cell line tumourspheres and primary mammospheres are not homogenous entities enriched for stem cells, suggesting a more cautious approach to interpreting data from these assays and careful consideration of its limitations. Sphere culture may represent an alternative 3-dimensional culture system which rather than universally ‘enriching’ for stem cells, has utility as one of a suite of functional assays that provide a read-out of progenitor activity. PMID:23750209

Neuregulin 1 Type II-ErbB Signaling Promotes Cell Divisions Generating Neurons from Neural Progenitor Cells in the Developing Zebrafish Brain.

PubMed

Sato, Tomomi; Sato, Fuminori; Kamezaki, Aosa; Sakaguchi, Kazuya; Tanigome, Ryoma; Kawakami, Koichi; Sehara-Fujisawa, Atsuko

2015-01-01

Post-mitotic neurons are generated from neural progenitor cells (NPCs) at the expense of their proliferation. Molecular and cellular mechanisms that regulate neuron production temporally and spatially should impact on the size and shape of the brain. While transcription factors such as neurogenin1 (neurog1) and neurod govern progression of neurogenesis as cell-intrinsic mechanisms, recent studies show regulatory roles of several cell-extrinsic or intercellular signaling molecules including Notch, FGF and Wnt in production of neurons/neural progenitor cells from neural stem cells/radial glial cells (NSCs/RGCs) in the ventricular zone (VZ). However, it remains elusive how production of post-mitotic neurons from neural progenitor cells is regulated in the sub-ventricular zone (SVZ). Here we show that newborn neurons accumulate in the basal-to-apical direction in the optic tectum (OT) of zebrafish embryos. While neural progenitor cells are amplified by mitoses in the apical ventricular zone, neurons are exclusively produced through mitoses of neural progenitor cells in the sub-basal zone, later in the sub-ventricular zone, and accumulate apically onto older neurons. This neurogenesis depends on Neuregulin 1 type II (NRG1-II)-ErbB signaling. Treatment with an ErbB inhibitor, AG1478 impairs mitoses in the sub-ventricular zone of the optic tectum. Removal of AG1478 resumes sub-ventricular mitoses without precedent mitoses in the apical ventricular zone prior to basal-to-apical accumulation of neurons, suggesting critical roles of ErbB signaling in mitoses for post-mitotic neuron production. Knockdown of NRG1-II impairs both mitoses in the sub-basal/sub-ventricular zone and the ventricular zone. Injection of soluble human NRG1 into the developing brain ameliorates neurogenesis of NRG1-II-knockdown embryos, suggesting a conserved role of NRG1 as a cell-extrinsic signal. From these results, we propose that NRG1-ErbB signaling stimulates cell divisions generating neurons from neural progenitor cells in the developing vertebrate brain.

Collagen VI Ablation Retards Brain Tumor Progression Due to Deficits in Assembly of the Vascular Basal Lamina

PubMed Central

You, Weon-Kyoo; Bonaldo, Paolo; Stallcup, William B.

2012-01-01

To investigate the importance of the vascular basal lamina in tumor blood vessel morphogenesis and function, we compared vessel development, vessel function, and progression of B16F10 melanoma tumors in the brains of wild-type and collagen VI-null mice. In 7-day tumors in the absence of collagen VI, the width of the vascular basal lamina was reduced twofold. Although the ablation of collagen VI did not alter the abundance of blood vessels, a detailed analysis of the number of either pericytes or endothelial cells (or pericyte coverage of endothelial cells) showed that collagen VI-dependent defects during the assembly of the basal lamina have negative effects on both pericyte maturation and the sprouting and survival of endothelial cells. As a result of these deficits, vessel patency was reduced by 25%, and vessel leakiness was increased threefold, resulting in a 10-fold increase in tumor hypoxia along with a fourfold increase in hypoxia-inducible factor-1α expression. In 12-day collagen VI-null tumors, vascular endothelial growth factor expression was increased throughout the tumor stroma, in contrast to the predominantly vascular pattern of vascular endothelial growth factor expression in wild-type tumors. Vessel size was correspondingly reduced in 12-day collagen VI-null tumors. Overall, these vascular deficits produced a twofold decrease in tumor volume in collagen VI-null mice, confirming that collagen VI-dependent basal lamina assembly is a critical aspect of vessel development. PMID:22200614

A Small Molecule Inverse Agonist for the Human Thyroid-Stimulating Hormone Receptor

PubMed Central

Neumann, Susanne; Huang, Wenwei; Eliseeva, Elena; Titus, Steve; Thomas, Craig J.; Gershengorn, Marvin C.

2010-01-01

Small molecule inverse agonists for the TSH receptor (TSHR) may be used as probes of the role of basal (or agonist-independent or constitutive) signaling and may have therapeutic potential as orally active drugs to inhibit basal signaling in patients with thyroid cancer and in some patients with hyperthyroidism. We describe the first small-molecule ligand [1;2-(3-((2,6-dimethylphenoxy)methyl)-4-methoxyphenyl)-3-(furan-2-ylmethyl)-2,3-dihydroquinazolin-4(1H)-one] that exhibits inverse agonist properties at TSHR. 1 inhibits basal and TSH-stimulated signaling, measured as cAMP production, by TSHRs in HEK-EM 293 cells stably expressing wild-type TSHRs; the antagonism of TSH-mediated signaling is competitive. 1 also inhibits basal signaling by wild-type TSHRs, and four constitutively active mutants of TSHR expressed transiently in HEK-EM 293 cells. 1 was active under more physiologically relevant conditions in primary cultures of human thyrocytes expressing endogenous TSHRs where it inhibited basal levels of mRNA transcripts for thyroglobulin, thyroperoxidase, sodium iodide symporter, and TSHR. These data serve as proof of principle that small, drug-like molecules can inhibit basal signaling by TSHR. We suggest that this small molecule is a lead compound for the development of higher-potency inverse agonists that can be used as probes of TSHR biology with therapeutic potential. PMID:20427476

A Novel Modelling Approach for Predicting Forest Growth and Yield under Climate Change.

PubMed

Ashraf, M Irfan; Meng, Fan-Rui; Bourque, Charles P-A; MacLean, David A

2015-01-01

Global climate is changing due to increasing anthropogenic emissions of greenhouse gases. Forest managers need growth and yield models that can be used to predict future forest dynamics during the transition period of present-day forests under a changing climatic regime. In this study, we developed a forest growth and yield model that can be used to predict individual-tree growth under current and projected future climatic conditions. The model was constructed by integrating historical tree growth records with predictions from an ecological process-based model using neural networks. The new model predicts basal area (BA) and volume growth for individual trees in pure or mixed species forests. For model development, tree-growth data under current climatic conditions were obtained using over 3000 permanent sample plots from the Province of Nova Scotia, Canada. Data to reflect tree growth under a changing climatic regime were projected with JABOWA-3 (an ecological process-based model). Model validation with designated data produced model efficiencies of 0.82 and 0.89 in predicting individual-tree BA and volume growth. Model efficiency is a relative index of model performance, where 1 indicates an ideal fit, while values lower than zero means the predictions are no better than the average of the observations. Overall mean prediction error (BIAS) of basal area and volume growth predictions was nominal (i.e., for BA: -0.0177 cm(2) 5-year(-1) and volume: 0.0008 m(3) 5-year(-1)). Model variability described by root mean squared error (RMSE) in basal area prediction was 40.53 cm(2) 5-year(-1) and 0.0393 m(3) 5-year(-1) in volume prediction. The new modelling approach has potential to reduce uncertainties in growth and yield predictions under different climate change scenarios. This novel approach provides an avenue for forest managers to generate required information for the management of forests in transitional periods of climate change. Artificial intelligence technology has substantial potential in forest modelling.

A Novel Modelling Approach for Predicting Forest Growth and Yield under Climate Change

PubMed Central

Ashraf, M. Irfan; Meng, Fan-Rui; Bourque, Charles P.-A.; MacLean, David A.

2015-01-01

Global climate is changing due to increasing anthropogenic emissions of greenhouse gases. Forest managers need growth and yield models that can be used to predict future forest dynamics during the transition period of present-day forests under a changing climatic regime. In this study, we developed a forest growth and yield model that can be used to predict individual-tree growth under current and projected future climatic conditions. The model was constructed by integrating historical tree growth records with predictions from an ecological process-based model using neural networks. The new model predicts basal area (BA) and volume growth for individual trees in pure or mixed species forests. For model development, tree-growth data under current climatic conditions were obtained using over 3000 permanent sample plots from the Province of Nova Scotia, Canada. Data to reflect tree growth under a changing climatic regime were projected with JABOWA-3 (an ecological process-based model). Model validation with designated data produced model efficiencies of 0.82 and 0.89 in predicting individual-tree BA and volume growth. Model efficiency is a relative index of model performance, where 1 indicates an ideal fit, while values lower than zero means the predictions are no better than the average of the observations. Overall mean prediction error (BIAS) of basal area and volume growth predictions was nominal (i.e., for BA: -0.0177 cm2 5-year-1 and volume: 0.0008 m3 5-year-1). Model variability described by root mean squared error (RMSE) in basal area prediction was 40.53 cm2 5-year-1 and 0.0393 m3 5-year-1 in volume prediction. The new modelling approach has potential to reduce uncertainties in growth and yield predictions under different climate change scenarios. This novel approach provides an avenue for forest managers to generate required information for the management of forests in transitional periods of climate change. Artificial intelligence technology has substantial potential in forest modelling. PMID:26173081

Lectins stain cells differentially in the coral, Montipora capitata

USGS Publications Warehouse

Work, Thierry M.; Farah, Yael

2014-01-01

A limitation in our understanding of coral disease pathology and cellular pathogenesis is a lack of reagents to characterize coral cells. We evaluated the utility of plant lectins to stain tissues of a dominant coral, Montipora capitata, from Hawaii. Of 22 lectins evaluated, nine of these stained structures in the upper or basal body wall of corals. Specific structures revealed by lectins that were not considered distinct or evident on routine hematoxylin and eosin sections of coral tissues included apical and basal granules in gastrodermis and epidermis, cnidoglandular tract and actinopharynx cell surface membranes, capsules of mature holotrichous isorhizas, and perivitelline and periseminal cells. Plant lectins could prove useful to further our understanding of coral physiology, anatomy, cell biology, and disease pathogenesis.

Theoretical estimates of mechanical properties of the endothelial cell cytoskeleton.

PubMed Central

Satcher, R L; Dewey, C F

1996-01-01

Current modeling of endothelial cell mechanics does not account for the network of F-actin that permeates the cytoplasm. This network, the distributed cytoplasmic structural actin (DCSA), extends from apical to basal membranes, with frequent attachments. Stress fibers are intercalated within the network, with similar frequent attachments. The microscopic structure of the DCSA resembles a foam, so that the mechanical properties can be estimated with analogy to these well-studied systems. The moduli of shear and elastic deformations are estimated to be on the order of 10(5) dynes/cm2. This prediction agrees with experimental measurements of the properties of cytoplasm and endothelial cells reported elsewhere. Stress fibers can potentially increase the modulus by a factor of 2-10, depending on whether they act in series or parallel to the network in transmitting surface forces. The deformations produced by physiological flow fields are of insufficient magnitude to disrupt cell-to-cell or DCSA cross-linkages. The questions raised by this paradox, and the ramifications of implicating the previously unreported DCSA as the primary force transmission element are discussed. Images FIGURE 2 PMID:8804594

Concerted evolution of body mass and cell size: similar patterns among species of birds (Galliformes) and mammals (Rodentia)

PubMed Central

Dragosz-Kluska, Dominika; Pis, Tomasz; Pawlik, Katarzyna; Kapustka, Filip; Kilarski, Wincenty M.; Kozłowski, Jan

2018-01-01

ABSTRACT Cell size plays a role in body size evolution and environmental adaptations. Addressing these roles, we studied body mass and cell size in Galliformes birds and Rodentia mammals, and collected published data on their genome sizes. In birds, we measured erythrocyte nuclei and basal metabolic rates (BMRs). In birds and mammals, larger species consistently evolved larger cells for five cell types (erythrocytes, enterocytes, chondrocytes, skin epithelial cells, and kidney proximal tubule cells) and evolved smaller hepatocytes. We found no evidence that cell size differences originated through genome size changes. We conclude that the organism-wide coordination of cell size changes might be an evolutionarily conservative characteristic, and the convergent evolutionary body size and cell size changes in Galliformes and Rodentia suggest the adaptive significance of cell size. Recent theory predicts that species evolving larger cells waste less energy on tissue maintenance but have reduced capacities to deliver oxygen to mitochondria and metabolize resources. Indeed, birds with larger size of the abovementioned cell types and smaller hepatocytes have evolved lower mass-specific BMRs. We propose that the inconsistent pattern in hepatocytes derives from the efficient delivery system to hepatocytes, combined with their intense involvement in supracellular function and anabolic activity. PMID:29540429

Sensitivity, predictive values, pretest-posttest probabilities, and likelihood ratios of presurgery clinical diagnosis of nonmelanoma skin cancers.

PubMed

Ermertcan, Aylin Türel; Oztürk, Ferdi; Gençoğlan, Gülsüm; Eskiizmir, Görkem; Temiz, Peyker; Horasan, Gönül Dinç

2011-03-01

The precision of clinical diagnosis of skin tumors is not commonly measured and, therefore, very little is known about the diagnostic ability of clinicians. This study aimed to compare clinical and histopathologic diagnoses of nonmelanoma skin cancers with regard to sensitivity, predictive values, pretest-posttest probabilities, and likelihood ratios. Two hundred nineteen patients with 241 nonmelanoma skin cancers were enrolled in this study. Of these patients, 49.4% were female and 50.6% were male. The mean age ± standard deviation (SD) was 63.66 ± 16.44 years for the female patients and 64.77 ± 14.88 years for the male patients. The mean duration of the lesions was 20.90 ± 32.95 months. One hundred forty-eight (61.5%) of the lesions were diagnosed as basal cell carcinoma (BCC) and 93 (38.5%) were diagnosed as squamous cell carcinoma (SCC) histopathologically. Sensitivity, positive predictive value, and posttest probability were calculated as 75.96%, 87.77%, and 87.78% for BCC and 70.37%, 37.25%, and 37.20% for SCC, respectively. The correlation between clinical and histopathologic diagnoses was found to be higher in BCC. Knowledge of sensitivity, predictive values, likelihood ratios, and posttest probabilities may have implications for the management of skin cancers. To prevent unnecessary surgeries and achieve high diagnostic accuracies, multidisciplinary approaches are recommended.

A Semi-Supervised Approach for Refining Transcriptional Signatures of Drug Response and Repositioning Predictions

PubMed Central

Iorio, Francesco; Shrestha, Roshan L.; Levin, Nicolas; Boilot, Viviane; Garnett, Mathew J.; Saez-Rodriguez, Julio; Draviam, Viji M.

2015-01-01

We present a novel strategy to identify drug-repositioning opportunities. The starting point of our method is the generation of a signature summarising the consensual transcriptional response of multiple human cell lines to a compound of interest (namely the seed compound). This signature can be derived from data in existing databases, such as the connectivity-map, and it is used at first instance to query a network interlinking all the connectivity-map compounds, based on the similarity of their transcriptional responses. This provides a drug neighbourhood, composed of compounds predicted to share some effects with the seed one. The original signature is then refined by systematically reducing its overlap with the transcriptional responses induced by drugs in this neighbourhood that are known to share a secondary effect with the seed compound. Finally, the drug network is queried again with the resulting refined signatures and the whole process is carried on for a number of iterations. Drugs in the final refined neighbourhood are then predicted to exert the principal mode of action of the seed compound. We illustrate our approach using paclitaxel (a microtubule stabilising agent) as seed compound. Our method predicts that glipizide and splitomicin perturb microtubule function in human cells: a result that could not be obtained through standard signature matching methods. In agreement, we find that glipizide and splitomicin reduce interphase microtubule growth rates and transiently increase the percentage of mitotic cells–consistent with our prediction. Finally, we validated the refined signatures of paclitaxel response by mining a large drug screening dataset, showing that human cancer cell lines whose basal transcriptional profile is anti-correlated to them are significantly more sensitive to paclitaxel and docetaxel. PMID:26452147

In vivo confocal microscopy indicates an inverse relationship between the sub-basal corneal plexus and the conjunctivalisation in patients with limbal stem cell deficiency.

PubMed

Caro-Magdaleno, Manuel; Alfaro-Juárez, Asunción; Montero-Iruzubieta, Jesús; Fernández-Palacín, Ana; Muñoz-Morales, Ana; Castilla-Martino, Manuel Alberto; Spínola-Muñoz, Consuelo; Rodríguez-de-la-Rúa, Enrique

2018-05-18

Limbal stem cell deficiency (LSCD) is characterised by a marked decrease in limbal stem cells. It is classified primarily using subjective slit-lamp observations. In vivo confocal microscopy (IVCM) can non-invasively provide objective information on the condition of the limbal niche, the corneal epithelial basal cell density and the corneal sub-basal nerve plexus density (SND). We here used IVCM to evaluate changes in SND to improve LSCD classification. We evaluated and classified 38 patients (76 eyes, 44 with LSC and 32 control eyes) using the Rama, López-García and Deng (clinical and confocal) classifications and evaluated the concordance of the confocal and clinical classifications. We constructed a logistic regression model using multivariate analysis to correlate different degrees of conjunctivalisation with IVCM parameters and used receiver operating characteristic (ROC) curve analysis to establish the SND cut-off value with maximum diagnostic sensitivity and specificity. The classification systems correlated moderately at best (kappa, 0.449). The corneal SND of cases (6469±6295 µm/mm 2 ) was less (p<0.001) than in controls (20911±4142 µm/mm 2 ). The SND, but not basal cell density, played a protective role against conjunctivalisation (OR, 0.069; 95% CI 0.008-0.619; p=0.01). An SND cut-off value of 17 215 µm/mm 2 yielded a sensitivity and specificity of 95.5% and 90.6%, respectively, for LSCD diagnosis. The density of the corneal sub-basal nerve plexus was inversely related to conjunctivalisation in LSCD. Further studies are needed to verify this and to elucidate the directionality between these factors. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Squamous cell cancer (image)

MedlinePlus

Squamous cell cancer involves cancerous changes to the cells of the middle portion of the epidermal skin layer. It is ... malignant tumor, and is more aggressive than basal cell cancer, but still may be relatively slow-growing. It ...

Use of basal serum or plasma cortisol concentrations to rule out a diagnosis of hypoadrenocorticism in dogs: 123 cases (2000-2005).

PubMed

Lennon, Elizabeth M; Boyle, Tonya E; Hutchins, Rae Grace; Friedenthal, Arit; Correa, Maria T; Bissett, Sally A; Moses, Lorra S; Papich, Mark G; Birkenheuer, Adam J

2007-08-01

To determine whether basal serum or plasma cortisol concentration can be used as a screening test to rule out hypoadrenocorticism in dogs. Retrospective case-control study. 110 dogs with nonadrenal gland illnesses and 13 dogs with hypoadrenocorticism. Sensitivity and specificity of basal serum or plasma cortisol concentrations of either 2 microg/dL that are not receiving corticosteroids, mitotane, or ketoconazole are highly unlikely to have hypoadrenocorticism. However, if the basal cortisol concentration is

Retrieving Ice Basal Motion Using the Hydrologically Coupled JPL/UCI Ice Sheet System Model (ISSM)

NASA Astrophysics Data System (ADS)

Khakbaz, B.; Morlighem, M.; Seroussi, H. L.; Larour, E. Y.

2011-12-01

The study of basal sliding in ice sheets requires coupling ice-flow models with subglacial water flow. In fact, subglacial hydrology models can be used to model basal water-pressure explicitly and to generate basal sliding velocities. This study addresses the addition of a thin-film-based subglacial hydrologic module to the Ice Sheet System Model (ISSM) developed by JPL in collaboration with the University of California Irvine (UCI). The subglacial hydrology model follows the study of J. Johnson (2002) who assumed a non-arborscent distributed drainage system in the form of a thin film beneath ice sheets. The differential equation that arises from conservation of mass in the water system is solved numerically with the finite element method in order to obtain the spatial distribution of basal water over the study domain. The resulting sheet water thickness is then used to model the basal water-pressure and subsequently the basal sliding velocity. In this study, an introduction and preliminary results of the subglacial water flow and basal sliding velocity will be presented for the Pine Island Glacier west Antarctica.This work was performed at the California Institute of Technology's Jet Propulsion Laboratory under a contract with the National Aeronautics and Space Administration's Modeling, Analysis and Prediction (MAP) Program.

Skin lesion removal

MedlinePlus

... benign; Cryosurgery - skin, benign; BCC - removal; Basal cell cancer - removal; Actinic keratosis - removal; Wart - removal; Squamous cell - removal; Mole - removal; Nevus - removal; Nevi - removal; Scissor ...

Histopathologic pitfalls of Mohs micrographic surgery and a review of tumor histology.

PubMed

França, Katlein; Alqubaisy, Yasser; Hassanein, Ashraf; Nouri, Keyvan; Lotti, Torello

2018-06-01

Mohs micrographic surgery is a specialized subset of staged surgical excisions with each subsequent stage being driven largely by the histologic findings of the previous stage. Therefore, it is imperative that histologic analysis is performed in an accurate manner. Frozen section and tissue flattening is a crucial step in Mohs surgery. Frozen sections introduce certain artifacts and these artifacts must be interpreted in the correct context. Basal and squamous cell carcinomas are the most common tumors encountered in Mohs micrographic surgery, and their histopathology is also associated with certain "pitfalls". Basal cell carcinoma should be distinguished from hair follicles, folliculocentric basaloid proliferations, poromas, nevus sebaceous, desmoplastic trichoepitheliomas, and spiradenomas, to name but a few histologic entities. Similarly, squamous cell carcinoma should be distinguished from hypertrophic actinic keratoses, pseudoepitheliomatous hyperplasia, sebaceous carcinoma, and microcystic adnexal carcinoma. In addition, there are numerous subtypes of basal cell and squamous carcinomas that the Mohs surgeon should be aware of due to differences in the biologic behavior of these tumors. This review presents a number of the common histologic pitfalls of Mohs micrographic surgery and a review of tumor histology.

Essential Roles of Epithelial Bone Morphogenetic Protein Signaling During Prostatic Development

PubMed Central

Omori, Akiko; Miyagawa, Shinichi; Ogino, Yukiko; Harada, Masayo; Ishii, Kenichiro; Sugimura, Yoshiki; Ogino, Hajime; Nakagata, Naomi

2014-01-01

Prostate is a male sex-accessory organ. The prostatic epithelia consist primarily of basal and luminal cells that differentiate from embryonic urogenital sinus epithelia. Prostate tumors are believed to originate in the basal and luminal cells. However, factors that promote normal epithelial differentiation have not been well elucidated, particularly for bone morphogenetic protein (Bmp) signaling. This study shows that Bmp signaling prominently increases during prostatic differentiation in the luminal epithelia, which is monitored by the expression of phosphorylated Smad1/5/8. To elucidate the mechanism of epithelial differentiation and the function of Bmp signaling during prostatic development, conditional male mutant mouse analysis for the epithelial-specific Bmp receptor 1a (Bmpr1a) was performed. We demonstrate that Bmp signaling is indispensable for luminal cell maturation, which regulates basal cell proliferation. Expression of the prostatic epithelial regulatory gene Nkx3.1 was significantly reduced in the Bmpr1a mutants. These results indicate that Bmp signaling is a key factor for prostatic epithelial differentiation, possibly by controlling the prostatic regulatory gene Nkx3.1. PMID:24731097

Fine structure of the ependyma and intercellular junctions in the area postrema of the rat.

PubMed

Gotow, T; Hashimoto, P H

1979-09-03

Ependymal cells and their junctional complexes in the area postrema of the rat were studied in detail by tracer experiments using horseradish peroxidase (HRP) and colloidal lanthanum and by freeze-etch techniques, in addition to routine electron microscopy. The ependyma of the area postrema is characterized as flattened cells possessing very few cilia, a moderate amount of microvilli, a well-developed Golgi apparatus and rough endoplasmic reticulum. Numerous vesicles or tubular formations with internal dense content were found to accumulate in the basal processes of ependymal cells; the basal process makes contact with the perivascular basal lamina. It is suggested that the dense material in the tubulovesicular formations is synthesized within the ependymal cell and discharged into the perivascular space. The apical junctions between adjacent ependymal cells display very close apposition, with a gap of 2--3 nm, but no fusion of adjacent plasma membranes; they thus represent a transitional form between the zonulae adhaerentes present in the ordinary mural ependyma and the zonulae occludentes in the choroidal epithelium. A direct intercommunication between the ventricular cerebrospinal fluid (CSF) and the blood vascular system indicates that a region exists lacking a blood-ventricular CSF barrier.

Microsurgical removal of epidermal and cortical cells: evidence that the gravitropic signal moves through the outer cell layers in primary roots of maize

NASA Technical Reports Server (NTRS)

Yang, R. L.; Evans, M. L.; Moore, R.

1990-01-01

There is general agreement that during root gravitropism some sort of growth-modifying signal moves from the cap to the elongation zone and that this signal ultimately induces the curvature that leads to reorientation of the root. However, there is disagreement regarding both the nature of the signal and the pathway of its movement from the root cap to the elongation zone. We examined the pathway of movement by testing gravitropism in primary roots of maize (Zea mays L.) from which narrow (0.5 mm) rings of epidermal and cortical tissue were surgically removed from various positions within the elongation zone. When roots were girdled in the apical part of the elongation zone gravitropic curvature occurred apical to the girdle but not basal to the girdle. Filling the girdle with agar allowed curvature basal to the girdle to occur. Shallow girdles, in which only two or three cell layers (epidermis plus one or two cortical cell layers) were removed, prevented or greatly delayed gravitropic curvature basal to the girdle. The results indicate that the gravitropic signal moves basipetally through the outermost cell layers, perhaps through the epidermis itself.

Laminar Differences in Dendritic Structure of Pyramidal Neurons in the Juvenile Rat Somatosensory Cortex.

PubMed

Rojo, Concepción; Leguey, Ignacio; Kastanauskaite, Asta; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier; Benavides-Piccione, Ruth

2016-06-01

Pyramidal cell structure varies between different cortical areas and species, indicating that the cortical circuits that these cells participate in are likely to be characterized by different functional capabilities. Structural differences between cortical layers have been traditionally reported using either the Golgi method or intracellular labeling, but the structure of pyramidal cells has not previously been systematically analyzed across all cortical layers at a particular age. In the present study, we investigated the dendritic architecture of complete basal arbors of pyramidal neurons in layers II, III, IV, Va, Vb, and VI of the hindlimb somatosensory cortical region of postnatal day 14 rats. We found that the characteristics of basal dendritic morphologies are statistically different in each cortical layer. The variations in size and branching pattern that exist between pyramidal cells of different cortical layers probably reflect the particular functional properties that are characteristic of the cortical circuit in which they participate. This new set of complete basal dendritic arbors of 3D-reconstructed pyramidal cell morphologies across each cortical layer will provide new insights into interlaminar information processing in the cerebral cortex. © The Author 2016. Published by Oxford University Press.

Human eccrine sweat gland cells reconstitute polarized spheroids when subcutaneously implanted with Matrigel in nude mice.

PubMed

Li, Haihong; Zhang, Mingjun; Chen, Liyun; Li, Xuexue; Zhang, Bingna

2016-10-01

Increasing evidence indicates that maintenance of cell polarity plays a pivotal role in the regulation of glandular homeostasis and function. We examine the markers for polarity at different time points to investigate the formation of cell polarity during 3D reconstitution of eccrine sweat glands. Mixtures of eccrine sweat gland cells and Matrigel were injected subcutaneously into the inguinal regions of nude mice. At 2, 3, 4, 5 and 6 weeks post-implantation, Matrigel plugs were removed and immunostained for basal collagen IV, lateral β-catenin, lateroapical ZO-1 and apical F-actin. The results showed that the cell polarity of the spheroids appeared in sequence. Formation of basal polarity was prior to lateral, apical and lateroapical polarity. Collagen IV was detected basally at 2 weeks, β-catenin laterally and ZO-1 lateroapically at 3 weeks, and F-actin apically at 4 weeks post-implantation. At week 5 and week 6, the localization and the positive percentage of collagen IV, β-catenin, ZO-1 or F-actin in spheroids was similar to that in native eccrine sweat glands. We conclude that the reconstituted 3D eccrine sweat glands are functional or potentially functional.

L-lysine in Treating Oral Mucositis in Patients Undergoing Radiation Therapy With or Without Chemotherapy For Head and Neck Cancer

ClinicalTrials.gov

2013-05-15

Mucositis; Oral Complications of Chemotherapy; Oral Complications of Radiation Therapy; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Adenoid Cystic Carcinoma of the Oral Cavity; Stage I Basal Cell Carcinoma of the Lip; Stage I Lymphoepithelioma of the Nasopharynx; Stage I Lymphoepithelioma of the Oropharynx; Stage I Mucoepidermoid Carcinoma of the Oral Cavity; Stage I Salivary Gland Cancer; Stage I Squamous Cell Carcinoma of the Hypopharynx; Stage I Squamous Cell Carcinoma of the Larynx; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Nasopharynx; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Verrucous Carcinoma of the Larynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Adenoid Cystic Carcinoma of the Oral Cavity; Stage II Basal Cell Carcinoma of the Lip; Stage II Lymphoepithelioma of the Nasopharynx; Stage II Lymphoepithelioma of the Oropharynx; Stage II Mucoepidermoid Carcinoma of the Oral Cavity; Stage II Salivary Gland Cancer; Stage II Squamous Cell Carcinoma of the Hypopharynx; Stage II Squamous Cell Carcinoma of the Larynx; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Larynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage III Basal Cell Carcinoma of the Lip; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Lymphoepithelioma of the Oropharynx; Stage III Mucoepidermoid Carcinoma of the Oral Cavity; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Lymphoepithelioma of the Oropharynx; Stage IV Mucoepidermoid Carcinoma of the Oral Cavity; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity

Marine ice sheet model performance depends on basal sliding physics and sub-shelf melting

NASA Astrophysics Data System (ADS)

Gladstone, Rupert Michael; Warner, Roland Charles; Galton-Fenzi, Benjamin Keith; Gagliardini, Olivier; Zwinger, Thomas; Greve, Ralf

2017-01-01

Computer models are necessary for understanding and predicting marine ice sheet behaviour. However, there is uncertainty over implementation of physical processes at the ice base, both for grounded and floating glacial ice. Here we implement several sliding relations in a marine ice sheet flow-line model accounting for all stress components and demonstrate that model resolution requirements are strongly dependent on both the choice of basal sliding relation and the spatial distribution of ice shelf basal melting.Sliding relations that reduce the magnitude of the step change in basal drag from grounded ice to floating ice (where basal drag is set to zero) show reduced dependence on resolution compared to a commonly used relation, in which basal drag is purely a power law function of basal ice velocity. Sliding relations in which basal drag goes smoothly to zero as the grounding line is approached from inland (due to a physically motivated incorporation of effective pressure at the bed) provide further reduction in resolution dependence.A similar issue is found with the imposition of basal melt under the floating part of the ice shelf: melt parameterisations that reduce the abruptness of change in basal melting from grounded ice (where basal melt is set to zero) to floating ice provide improved convergence with resolution compared to parameterisations in which high melt occurs adjacent to the grounding line.Thus physical processes, such as sub-glacial outflow (which could cause high melt near the grounding line), impact on capability to simulate marine ice sheets. If there exists an abrupt change across the grounding line in either basal drag or basal melting, then high resolution will be required to solve the problem. However, the plausible combination of a physical dependency of basal drag on effective pressure, and the possibility of low ice shelf basal melt rates next to the grounding line, may mean that some marine ice sheet systems can be reliably simulated at a coarser resolution than currently thought necessary.

Gorlin-Goltz syndrome: A series of three cases.

PubMed

Patankar, Amod P; Kshirsagar, Rajesh A; Dugal, Arun; Mishra, Akshay; Ram, Hari

2014-01-01

The Gorlin-Goltz syndrome (GGS) is also known as nevoid basal cell carcinoma syndrome. It is characterized by multiple keratocystic odontogenic tumors (KCOTs) in the jaw, multiple basal cell nevi carcinomas and skeletal abnormities. The syndrome may be diagnosed early by a dentist during the routine radiographic exams in the first decade of life, since the KCOTs are usually one of the first manifestations of the syndrome. This article reports the series of 3 cases, emphasizing its clinical and radiographic manifestations of GGS.

Gorlin-Goltz syndrome: A series of three cases

PubMed Central

Patankar, Amod P.; Kshirsagar, Rajesh A.; Dugal, Arun; Mishra, Akshay; Ram, Hari

2014-01-01

The Gorlin-Goltz syndrome (GGS) is also known as nevoid basal cell carcinoma syndrome. It is characterized by multiple keratocystic odontogenic tumors (KCOTs) in the jaw, multiple basal cell nevi carcinomas and skeletal abnormities. The syndrome may be diagnosed early by a dentist during the routine radiographic exams in the first decade of life, since the KCOTs are usually one of the first manifestations of the syndrome. This article reports the series of 3 cases, emphasizing its clinical and radiographic manifestations of GGS. PMID:25937738

Surgical management of Gorlin syndrome: a 4-decade experience using local excision technique.

PubMed

Griner, Devan; Sutphin, Daniel; Sargent, Larry A

2015-04-01

Basal cell nevus syndrome (aka Gorlin syndrome, Gorlin-Goltz syndrome, nevoid basal cell carcinoma syndrome, and fifth phacomatosis) is a rare but well-described autosomal dominant condition with variable penetrance. We present a female patient who has been successfully treated using local surgical excision and diligent skin surveillance for more than 4 decades, demonstrating that simple local incision is an efficacious and reasonable surgical alternative that may circumvent the specialization and expense of Mohs technique.

Autofluorescence imaging of basal cell carcinoma by smartphone RGB camera

NASA Astrophysics Data System (ADS)

Lihachev, Alexey; Derjabo, Alexander; Ferulova, Inesa; Lange, Marta; Lihacova, Ilze; Spigulis, Janis

2015-12-01

The feasibility of smartphones for in vivo skin autofluorescence imaging has been investigated. Filtered autofluorescence images from the same tissue area were periodically captured by a smartphone RGB camera with subsequent detection of fluorescence intensity decreasing at each image pixel for further imaging the planar distribution of those values. The proposed methodology was tested clinically with 13 basal cell carcinoma and 1 atypical nevus. Several clinical cases and potential future applications of the smartphone-based technique are discussed.

Nevoid basal cell carcinoma syndrome in a black child.

PubMed

Hall, J; Johnston, K A; McPhillips, J P; Barnes, S D; Elston, D M

1998-02-01

Nevoid basal cell carcinoma syndrome (NBCCS) is rare in black persons. We describe an 11-year-old black boy with NBCCS who presented with exotropia and a painful, expanding, cystic mass in the left posterior alveolar ridge. Further examination revealed odontogenic keratocysts with palmar and plantar pitting. Less than 5% of reported patients with NBCCS are black. To our knowledge, this is the first report of a black patient with NBCCS presenting with exotropia and an impacted molar displaced into the orbit by an odontogenic keratocyst.

Autofluorescence imaging of basal cell carcinoma by smartphone RGB camera.

PubMed

Lihachev, Alexey; Derjabo, Alexander; Ferulova, Inesa; Lange, Marta; Lihacova, Ilze; Spigulis, Janis

2015-01-01

The feasibility of smartphones for in vivo skin autofluorescence imaging has been investigated. Filtered autofluorescence images from the same tissue area were periodically captured by a smartphone RGB camera with subsequent detection of fluorescence intensity decreasing at each image pixel for further imaging the planar distribution of those values. The proposed methodology was tested clinically with 13 basal cell carcinoma and 1 atypical nevus. Several clinical cases and potential future applications of the smartphone-based technique are discussed.

Functional genomic mRNA profiling of a large cancer data base demonstrates mesothelin overexpression in a broad range of tumor types.

PubMed

Lamberts, Laetitia E; de Groot, Derk Jan A; Bense, Rico D; de Vries, Elisabeth G E; Fehrmann, Rudolf S N

2015-09-29

The membrane bound glycoprotein mesothelin (MSLN) is a highly specific tumor marker, which is currently exploited as target for drugs. There are only limited data available on MSLN expression by human tumors. Therefore we determined overexpression of MSLN across different tumor types with Functional Genomic mRNA (FGM) profiling of a large cancer database. Results were compared with data in articles reporting immunohistochemical (IHC) MSLN tumor expression. FGM profiling is a technique that allows prediction of biologically relevant overexpression of proteins from a robust data set of mRNA microarrays. This technique was used in a database comprising 19,746 tumors to identify for 41 tumor types the percentage of samples with an overexpression of MSLN compared to a normal background. A literature search was performed to compare the FGM profiling data with studies reporting IHC MSLN tumor expression. FGM profiling showed MSLN overexpression in gastrointestinal (12-36%) and gynecological tumors (20-66%), non-small cell lung cancer (21%) and synovial sarcomas (30%). The overexpression found in thyroid cancers (5%) and renal cell cancers (10%) was not yet reported with IHC analyses. We observed that MSLN amplification rate within esophageal cancer depends on the histotype (31% for adenocarcinomas versus 3% for squamous-cell carcinomas). Subset analysis in breast cancer showed MSLN amplification rates of 28% in triple-negative breast cancer (TNBC) and 33% in basal-like breast cancer. Further subtype analysis of TNBCs showed the highest amplification rate (42%) in the basal-like 1 subtype and the lowest amplification rate (9%) in the luminal androgen receptor subtype.

Evaluating Forest Vegetation Simulator predictions for southern Appalachian upland hardwoods with a modified mortality model

Treesearch

Philip J. Radtke; Nathan D. Herring; David L. Loftis; Chad E. Keyser

2012-01-01

Prediction accuracy for projected basal area and trees per acre was assessed for the growth and yield model of the Forest Vegetation Simulator Southern Variant (FVS-Sn). Data for comparison with FVS-Sn predictions were compiled from a collection of n

SN56 neuronal cell death after 24 h and 14 days chlorpyrifos exposure through glutamate transmission dysfunction, increase of GSK-3β enzyme, β-amyloid and tau protein levels.

PubMed

Moyano, Paula; Frejo, María Teresa; Anadon, María José; García, José Manuel; Díaz, María Jesús; Lobo, Margarita; Sola, Emma; García, Jimena; Del Pino, Javier

2018-06-01

Chlorpyrifos (CPF) is an organophosphate insecticide described to induce cognitive disorders, both after acute and repeated administration. However, the mechanisms through which it induces these effects are unknown. CPF has been reported to produce basal forebrain cholinergic neuronal cell death, involved on learning and memory regulation, which could be the cause of such cognitive disorders. Neuronal cell death was partially mediated by oxidative stress generation, P75 NTR and α 7 -nAChRs gene expression alteration triggered through acetylcholinesterase (AChE) variants disruption, suggesting other mechanisms are involved. In this regard, CPF induces Aβ and tau proteins production and activation of GSK3β enzyme and alters glutamatergic transmission, which have been related with basal forebrain cholinergic neuronal cell death and development of cognitive disorders. According to these data, we hypothesized that CPF induces basal forebrain cholinergic neuronal cell death through induction of Aβ and tau proteins production, activation of GSK-3β enzyme and disruption of glutamatergic transmission. We evaluated this hypothesis in septal SN56 basal forebrain cholinergic neurons, after 24 h and 14 days CPF exposure. This study shows that CPF increases glutamate levels, upregulates GSK-3β gene expression, and increases the production of Aβ and phosphorylated tau proteins and all these effects reduced cell viability. CPF increases glutaminase activity and upregulates the VGLUT1 gene expression, which could mediate the disruption of glutamatergic transmission. Our present results provide new understanding of the mechanisms contributing to the harmful effects of CPF, and its possible relevance in the pathogenesis of neurodegenerative diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

The Epithelial Cell Adhesion Molecule EpCAM Is Required for Epithelial Morphogenesis and Integrity during Zebrafish Epiboly and Skin Development

PubMed Central

Slanchev, Krasimir; Carney, Thomas J.; Stemmler, Marc P.; Koschorz, Birgit; Amsterdam, Adam; Schwarz, Heinz; Hammerschmidt, Matthias

2009-01-01

The aberrant expression of the transmembrane protein EpCAM is associated with tumor progression, affecting different cellular processes such as cell–cell adhesion, migration, proliferation, differentiation, signaling, and invasion. However, the in vivo function of EpCAM still remains elusive due to the lack of genetic loss-of-function studies. Here, we describe epcam (tacstd) null mutants in zebrafish. Maternal-zygotic mutants display compromised basal protrusive activity and epithelial morphogenesis in cells of the enveloping layer (EVL) during epiboly. In partial redundancy with E-cadherin (Ecad), EpCAM made by EVL cells is further required for cell–cell adhesion within the EVL and, possibly, for proper attachment of underlying deep cells to the inner surface of the EVL, thereby also affecting deep cell epiboly movements. During later development, EpCAM per se becomes indispensable for epithelial integrity within the periderm of the skin, secondarily leading to disrupted morphology of the underlying basal epidermis and moderate hyper-proliferation of skin cells. On the molecular level, EVL cells of epcam mutant embryos display reduced levels of membranous Ecad, accompanied by an enrichment of tight junction proteins and a basal extension of apical junction complexes (AJCs). Our data suggest that EpCAM acts as a partner of E-cadherin to control adhesiveness and integrity as well as plasticity and morphogenesis within simple epithelia. In addition, EpCAM is required for the interaction of the epithelia with underlying cell layers. PMID:19609345

The Role of Basal Forebrain in Rat Somatosensory Cortex: Impact on Cholinergic Innervation, Sensory Information Processing, and Tactile Discrimination

DTIC Science & Technology

1993-05-28

1993 Dissertation and Abstract Approved: Commit tee Chairperson . ,a..w ember ~tee Member tli:u., ;2 9" PQ3 bate Date bate The author...1982; Mesulam et al., 1983; Rye et al., 1984; Saper, 1984). I will refer to the region of the basal forebrain that supplies cholinergic innervation to...topographical organization has been observed for cholinergic projection patterns, with more rostral and medial basal forebrain cell groups supplying

Serum Fetuin-A Levels in Patients with Bilateral Basal Ganglia Calcification.

PubMed

Demiryurek, Bekir Enes; Gundogdu, Asli Aksoy

2018-02-14

The idiopathic basal ganglia calcification (Fahr syndrome) may occur due to senility. Fetuin-A is a negative acute phase reactant which inhibits calcium-phosphorus precipitation and vascular calcification. In this study, we aimed to evaluate whether serum fetuin-A levels correlate with bilateral basal ganglia calcification. Forty-five patients who had bilateral basal ganglia calcification on brain CT were selected according to the inclusion and exclusion criteria, and 45 age and gender-matched subjects without basal ganglia calcification were included for the control group. Serum fetuin-A levels were measured from venous blood samples. All participants were divided into two groups; with and without basal ganglia calcification. These groups were divided into subgroups regarding age (18-32 and 33-45 years of age) and gender (male, female). We detected lower levels of serum fetuin-A in patients with basal ganglia calcification compared with the subjects without basal ganglia calcification. In all subgroups (female, male, 18-32 years and 33-45 years), mean fetuin-A levels were significantly lower in patients with basal ganglia calcification (p = 0.017, p = 0.014, p = 0.024, p = 0.026, p = 0.01 respectively). And statistically significantly lower levels of fetuin-A was found to be correlated with the increasing densities of calcification in the calcified basal ganglia group (p-value: <0.001). Considering the role of fetuin-A in tissue calcification and inflammation, higher serum fetuin-A levels should be measured in patients with basal ganglia calcification. We believe that the measurement of serum fetuin-A may play a role in the prediction of basal ganglia calcification as a biomarker. Copyright © 2017 Elsevier B.V. All rights reserved.

Reassessment of the structural basis of the ascending arousal system

PubMed Central

Fuller, Patrick M.; Sherman, David; Pedersen, Nigel P.; Saper, Clifford B.; Lu, Jun

2011-01-01

The “ascending reticular activating system” theory proposed that neurons in the upper brainstem reticular formation projected to forebrain targets that promoted wakefulness. More recent formulations have emphasized that most neurons at the pontomesencepahlic junction that participate in these pathways are actually in monoaminergic and cholinergic cell groups. However, cell-specific lesions of these cell groups have never been able to reproduce the deep coma seen after acute paramedian midbrain lesions that transect ascending axons at the caudal midbrain level. To determine whether the cortical afferents from the thalamus or the basal forebrain were more important in maintaining arousal, we first place large cell-body specific lesions in these targets. Surprisingly, extensive thalamic lesions had little effect on EEG or behavioral measures of wakefulness or on c-Fos expression by cortical neurons during wakefulness. In contrast, animals with large basal forebrain lesions were behaviorally unresponsive, had a monotonous sub-1 Hz EEG, and little cortical c-Fos expression during continuous gentle handling. We then retrogradely labeled inputs to the basal forebrain from the upper brainstem, and found a substantial input from glutamatergic neurons in the parabrachial nucleus and adjacent pre-coeruleus area. Cell specific lesions of the parabrachial-precoeruleus complex produced behavioral unresponsiveness, a monotonous sub-1Hz cortical EEG, and loss of cortical c-Fos expression during gentle handling. These experiments indicate that in rats the reticulo-thalamo-cortical pathway may play a very limited role in behavioral or electrocortical arousal, while the projection from the parabrachial nucleus and precoeruleus region, relayed by the basal forebrain to the cerebral cortex, may be critical for this process. PMID:21280045

Basal Cell Carcinoma Arising within Seborrheic Keratosis

PubMed Central

Yurdakul, Cüneyt; Güçer, Hasan; Sehitoglu, Ibrahim

2014-01-01

Malignant tumour development within a seborrheic keratosis (SK) is extremely rare. Though the most commonly developed malignant tumour is the basal cell carcinoma (BCC), other tumour types have also been reported in literature. Herein, we will report a superficial type BCC case developed within SK localized in hairy skin of a 78-year-old female patient. In immunohistochemical evaluation, diffuse positive staining with CK19 and over-expression in p53 compared with non-neoplastic areas were determined in neoplastic basaloid islands. It is always not easy to differentiate especially superficial type BCC cases from non-neoplastic epithelium of SK with histopathological evaluation. As far as this reason we believe that in difficult differentiation of these 2 lesions, in order to show the differentiation in basal epithelium, immunohistochemical evaluation may be helpful. PMID:25177624