The cyclin-dependent kinase inhibitors p27Kip1 and p21WAF1/Cip1 play important roles in cell-cycle regulation. Although alterations of these genes have been linked to tumorigenesis of several human ...carcinomas, their involvement in head and neck squamous tumorigenesis is rarely investigated. To determine the role of these genes in the evolution of squamous carcinoma of the head and neck we evaluated their protein expression by immunohistochemistry in non-dysplastic squamous epithelium, premalignant lesions and oral squamous carcinomas. The p53 gene and Ki-67 expressions were correlated with traditional clinicopathologic variables. Our study shows that in histologically non-dysplastic squamous epithelium, p27 expression was noted mainly in superficial differentiated cells, whereas p21, p53 and Ki-67 staining was observed in basal and suprabasal cells. In dysplasia, divergent expression between p27 and p21 was observed: p27 precipitously decreased and p21, p53, and Ki-67 increased with histologic progression. In squamous carcinomas, p27 was mainly expressed in well differentiated tumor cell nests, while the expressions of p21, p53, and Ki-67 were variable in the poorly differentiated tumor areas. A significant inverse relationship between p27 expression and those of p21, p53, and Ki-67 was observed, but no significant association between any of these markers and clinicopathologic factors was noted in this cohort. Our study indicates that: i) down-regulation of p27 and up-regulation of p21 are associated with early progression of HNSC, ii) p21 expression correlates positively with proliferation while p27 correlates positively with cell differentiation and iii) concurrent p27 and p21 expression analysis may allow for better assessment of HNSC progression.
The U-PB dating of 18 samples, representing the principal rock types of the 4,000 km2 Salmi anorthosite-rapakivi granite complex and its satellite Uljalegi pluton, southeastern Baltic Shield, reveals ...that six temporally distinct episodes of igneous activity occurred in a timespan of 17 million years.
Histologic features of melanoma associated with CDKN2A genotype Sargen, Michael R., MD; Kanetsky, Peter A., PhD, MPH; Newton-Bishop, Julia, MD, FMedSci ...
Journal of the American Academy of Dermatology,
03/2015, Letnik:
72, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Background Inherited susceptibility genes have been associated with histopathologic characteristics of tumors. Objective We sought to identify associations between histology of melanomas and CDKN2A ...genotype. Methods This was a case-control study design comparing 28 histopathologic tumor features among individuals with sporadic melanomas (N = 81) and cases from melanoma families with (N = 123) and without (N = 120) CDKN2A germline mutations. Results Compared with CDKN2A− cases, mutation carriers tended to have histologic features of superficial spreading melanoma subtype including higher pigmentation ( Ptrend = .02) and increased pagetoid scatter ( Ptrend = .07) after adjusting for age at diagnosis, sex, and American Joint Committee on Cancer thickness category. Similar associations were observed when comparing mutation carriers with a combined group of CDKN2A− (wild type) and sporadic melanomas. The presence of spindle cell morphology in the vertical growth phase was also an important predictor of genotype. Of the 15 cases with this phenotype, none were observed to harbor a CDKN2A mutation. Limitations Our study examined rare mutations and may have been underpowered to detect small, but biologically significant associations between histology and genotype. Conclusion Familial melanomas with CDKN2A mutations preferentially express a histologic phenotype of dense pigmentation, high pagetoid scatter, and a non-spindle cell morphology in the vertical growth phase.
ABSTRACT We place statistical constraints on Type Ia supernova (SN Ia) progenitors using 227 nebular-phase spectra of 111 SNe Ia. We find no evidence of stripped companion emission in any of the ...nebular-phase spectra. Upper limits are placed on the amount of mass that could go undetected in each spectrum using recent hydrodynamic simulations. With these null detections, we place an observational 3σ upper limit on the fraction of SNe Ia that are produced through the classical H-rich non-degenerate companion scenario of $\lt 5.5 {{\ \rm per\ cent}}$. Additionally, we set a tentative 3σ upper limit otan He star progenitor scenarios of $\lt 6.4 {{\ \rm per\ cent}}$, although further theoretical modelling is required. These limits refer to our most representative sample including normal, 91bg-like, 91T-like, and ‘super-Chandrasekhar’ SNe Ia but excluding SNe Iax and SNe Ia-CSM. As part of our analysis, we also derive a Nebular Phase Phillips Relation, which approximates the brightness of an SN Ia from 150 to 500 d after maximum using the peak magnitude and decline rate parameter Δm15(B).
An experiment was done to investigate the interactive effects of photoperiod (12L:12D or 18L:6D) and feeding frequency on the growth of newly weaned Australian snapper (mean weight
=
0.14 g fish
−
1
...). Feeding frequency was investigated over 4 levels with 2 feeds delivered during the first half of the daylight period (2FE), 2 feeds during the latter half of the daylight period (2FL), 4 (4F) or 8 (8F) evenly spaced feeds per daylight period. Each treatment combination was replicated in 6 tanks and each tank was stocked with a biomass of 15 g tank
−
1
(i.e. approximately 108 fish tank
−
1
). Snapper were fed a constant ration of 10% BW day
−
1
for 32 days, which was adjusted during the experiment according to frequent weight check procedures. Fish that died were counted but not replaced.
Photoperiod, feeding frequency and the interaction of these factors significantly affected the individual harvest weight and thermal growth coefficient (TGC) of snapper. Interactions were driven by an increase in the magnitude of individual weight and TGC in snapper fed the 4F and 8F treatments and reared under the 18L:6D photoperiod, compared to snapper fed at the same frequencies but reared under the 12L:12D regime. Weight gain and TGC were best in snapper reared under a 18L:6D photoperiod regime and fed 8 feeds day
−
1
, however, weight gain did not plateau, suggesting further increases in weight gain may be possible if feeding frequencies greater then 8F are employed. Survival and apparent feed conversion ratio (AFCR) were significantly affected by feeding frequency alone, with significant improvements in snapper fed more frequently and in snapper fed twice daily but later in the same photoperiod (2FE
<
2FL
<
4F
<
8F). Size heterogeneity (measured by the coefficient of variation for individual harvest weight, CV
hw) was affected by photoperiod, and decreased significantly in snapper reared under the 18L:6D regime. Size heterogeneity was also affected by feeding frequency, however, only the CV
hw for snapper reared under the 8F feeding frequency was significantly lower than snapper fed at other rates (i.e. 2FE
=
2FL
=
4F
<
8F).
Snapper fed later in a photoperiod regime generally performed better than snapper fed earlier. Results from this study indicate that in order to maximize weight gain, survival and AFCR and to reduce size heterogeneity, newly weaned snapper should be reared under a 18L:6D photoperiod and, for fish fed 10% BW day
−
1
, fed 8 times day
−
1
.
► Three separate supracrustal successions in Madagascar have similar detrital modes. ► Based on detrital zircon ages, the successions were deposited between 1800 and 800
Ma. ► The successions occur ...on either side of a purported Neoproterozoic suture. ► Madagascar's Archaean blocks could have formed a coherent crustal entity.
New detrital zircon U–Pb age data obtained from various quartzite units of three spatially separated supracrustal packages in central and northern Madagascar, show that these units were deposited between 1.8 and 0.8
Ga and have similar aged provenances. The distribution of detrital zircon ages indicates an overwhelming contribution of sources with ages between 2.5 and 1.8
Ga. Possible source rocks with an age of 2.5
Ga are present in abundance in the crustal segments (Antananarivo, Antongil and Masora Domains) either side of a purported Neoproterozoic suture (“Betsimisaraka Suture Zone”). Recently, possible source rocks for the 1.8
Ga age peak have been recognised in southern Madagascar. All three supracrustal successions, as well as the Archaean blocks onto which they were emplaced, are intruded by mid-Neoproterozoic magmatic suites placing a minimum age on their deposition. The similarities in detrital pattern, maximum and minimum age of deposition in the three successions, lend some support to a model in which all of Madagascar's Archaean blocks form a coherent crustal entity (the Greater Dharwar Craton), rather than an amalgamate of disparate crustal blocks brought together only during Neoproterozoic convergence. However, potential source terranes exist outside Madagascar and on either side of the Neoproterozoic sutures, so that a model including a Neoproterozoic suture in Madagascar cannot be dispelled outright.
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