Epigenetic biomarkers in skin cancer Greenberg, Edward S; Chong, Kelly K; Huynh, Kelly T ...
Cancer letters,
01/2014, Letnik:
342, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Abstract Epigenetic aberrations have been associated with cutaneous melanoma tumorigenesis and progression including dysregulated DNA gene promoter region methylation, histone modification, and ...microRNA. Several of these major epigenetic aberrations have been developed into biomarkers. Epigenetic biomarkers can be detected in tissue and in blood as circulating DNA in melanoma patients. There is strong evidence that biomarkers in cutaneous melanoma will have an important role as companions to therapeutics and overall patient management. Important progress has been made in epigenetic melanoma biomarker development and verification of clinical utility, and this review discusses some of the key current developments and existing challenges.
•Kinetic parameters for co-pyrolysis of rubber residual and HDPE waste are obtained by DAEM.•Kinetic analysis is conducted using TGA equipment.•Pyrolysis of binary mixture of rubber residual and HDPE ...waste contained three stages.
The kinetic analysis for rubber residual i.e. rubber seed shell, high density polyethylene (HDPE) waste and its mixture are investigated using distributed activation energy model (DAEM) reaction model. Furthermore, the pyrolysis characteristics from these materials are investigated by non-isothermal thermogravimetric analysis from temperature 323 K to 1173 K at varying heating rates range of 10–200 K/min in inert argon atmosphere. The average value determined for activation energy, Ea and pre-exponential factor, k0 are 54.888 kJ mol−1 and 6.923 × 104 s−1 respectively for RSS, 75.396 kJ mol−1 and 1.346 × 106 s−1 respectively for HDPE and 64.010 kJ mol−1 and 8.444 × 104 s−1 respectively for binary mixture of RSS/HDPE. By taking these values as the initial guess for Gaussian distribution, and assuming the standard deviation, σ is at 15 kJ mol−1, as well as constant k0 value for all first order reactions, the mean activation energy, E0 determined from the distribution curve for RSS, HDPE and RSS/HDPE are 55.0 kJ mol−1, 75.5 kJ mol−1 and 64.0 kJ mol−1 respectively. The values of E0 and k0 in pyrolysis of binary mixture of RSS/HDPE are found to be lower compared to the individual component of RSS and HDPE in pyrolysis process.
The conundrum is as follows. Statute 1 offers the applicant a statutory right. Statute 2 allows the decision maker to create further subordinate legislation. If the subordinate legislation seeks to ...alter statute 1, we are possibly concerned with a Henry VIII clause. But what if the subordinate legislation stops short of altering statute 1, but only renders the statutory right under statute 1 practically difficult to exercise? This is the situation in 'R. (O) v Secretary of State for the Home Department' 2022 UKSC 3, 2022 2 W.L.R. 343. There section 1(4) of the British Nationality Act 1981 ("the 1981 Act") confers on certain individuals (including the applicant) a statutory right to apply to be registered as a British citizen. But this is subject to the payment of a registration fee. Section 68 of the Immigration Act 2014 ("the 2014 Act") empowers the Secretary of State to set the relevant level of the fee by way of subordinate legislation. This was done in the Immigration and Nationality (Fees) Regulations 2018, SI 2018/330 (the 2018 Regulations), which sets the fee for registration at 1 pounds,126 for an adult and 1 pounds,012 for a child, respectively. This fee meant that the applicant (amongst many others in a similar position) could not in practice exercise her rights under the 1981 Act. The applicant thus argued that the 2018 Regulations were 'ultra vires', for they "rendered nugatory the underlying statutory right to become a British citizen" (at 20-21). Lord Hodge (whose judgment commanded unanimous support of the court) ruled against the applicant. There were three components to His Lordship's reasoning, all of which deserve further attention.
Although Asian-descent men in the United States have been subjected to negative race-gender stereotyping and sexual racism, evidence suggests that mainstream perceptions and Asian American men’s ...self-definitions are in flux. Drawing on in-depth interviews of U.S.-born and -raised, middle-class, heterosexual Asian American men, supplemented by popular media textual analysis, we examine how these men are drawing upon a new form of alternative Asian American masculinity— one that we call “The Model Man”—in order to renegotiate their position within the present hierarchy of romantic preference. “The Model Man,” a hybrid masculinity construction that combines the elements of White hegemonic masculinity and model minority-based “Asian” masculinity, is co-opted and deployed by men as sexual/romantic capital—especially in relation to White women—because it enables the men to present themselves as desirable romantic partners. Although this masculinity strategy contains possibilities for further straitjacketing Asian American men via the model minority stereotype—and for re-inscribing heteronormativity and patriarchy/heterosexism—it may possess an unexpectedly subversive potential in allowing the men to contest their masculinity status and even remap hegemonic American manhood.
Aberrations in the methylation status of noncoding genomic repeat DNA sequences and specific gene promoter region are important epigenetic events in melanoma progression. Promoter methylation status ...in long interspersed nucleotide element-1 (LINE-1) and absent in melanoma-1 (AIM1;6q21) associated with melanoma progression and disease outcome was assessed. LINE-1 and AIM1 methylation status was assessed in paraffin-embedded archival tissue (PEAT; n=133) and in melanoma patients’ serum (n=56). LINE-1 U-Index (hypomethylation) and AIM1 were analyzed in microdissected melanoma PEAT sections. The LINE-1 U-Index of melanoma (n=100) was significantly higher than that of normal skin (n=14) and nevi (n=12; P=0.0004). LINE-1 U-Index level was elevated with increasing American Joint Committee on Cancer (AJCC) stage (P<0.0001). AIM1 promoter hypermethylation was found in higher frequency (P=0.005) in metastatic melanoma (65%) than in primary melanomas (38%). When analyzed, high LINE-1 U-Index and/or AIM1 methylation in melanomas were associated with disease-free survival (DFS) and overall survival (OS) in stage I/II patients (P=0.017 and 0.027, respectively). In multivariate analysis, melanoma AIM1 methylation status was a significant prognostic factor of OS (P=0.032). Furthermore, serum unmethylated LINE-1 was at higher levels in both stage III (n=20) and stage IV (n=36) patients compared with healthy donors (n=14; P=0.022). Circulating methylated AIM1 was detected in patients’ serum and was predictive of OS in stage IV patients (P=0.009). LINE-1 hypomethylation and AIM1 hypermethylation have prognostic utility in both melanoma patients’ tumors and serum.
"Asianness" under Construction Chong, Kelly H.
Sociological perspectives,
02/2017, Letnik:
60, Številka:
1
Journal Article
Recenzirano
Based on life-history interviews of interethnically married U.S.-raised Asians, this article examines the meaning and dynamics of Asian American interethnic marriages, and what they reveal about the ...complex incorporative process of this "in-between" racial minority group into the U.S.. In particular, this article explores the connection between Asian American interethnic marriage and pan-Asian consciousness/identity, both in terms of how panethnicity shapes romantic/marital desires of individuals and how pan-Asian culture and identity is invented and negotiated in the process of family-making. My findings indicate that while strong pan-Asian consciousness/identity underlies the connection among intermarried couples, these unions are not simply a defensive effort to "preserve" Asian-ethnic identity and cultur against a society that still racializes Asian Americans, but a tentative and often unpremeditated effort to navigate a path toward integration into the society through an ethnically based, albeit hybrid and reconstructed identity and culture, that helps the respondents retain the integrity of "Asianness."
BRAF mutations are frequent in cutaneous melanomas, and BRAF inhibitors (BRAFi) have shown remarkable clinical efficacy in BRAF mutant melanoma patients. However, acquired drug resistance can occur ...rapidly and tumor(s) often progresses thereafter. Various mechanisms of BRAFi resistance have recently been described; however, the mechanism of resistance remains controversial. In this study, we developed BRAFi-resistant melanoma cell lines and found that metastasis-related epithelial to mesenchymal transition properties of BRAFi-resistant cells were enhanced significantly. Upregulation of EGFR was observed in BRAFi-resistant cell lines and patient tumors because of demethylation of EGFR regulatory DNA elements. EGFR induced PI3K/AKT pathway activation in BRAFi-resistant cells through epigenetic regulation. Treatment of EGFR inhibitor was effective in BRAFi-resistant melanoma cell lines. The study demonstrates that EGFR epigenetic activation has important implications in BRAFi resistance in melanoma.
The study of multiracial people in the United States has typically focused on the experiences of Black–White racially-mixed individuals. In this article, we review and analyze the theoretical and ...evidence base for the White-leaning characterization of Asian–White multiracials. Historically, Asian Americans have been positioned as a “racial middle” group in relation to White and Black Americans. In line with this perceived racial position, Asian–White multiracials have been generally characterized as being more White than Black–White multiracials, as well as “leaning White” in terms of self-identification. While there is growing recognition of the variability of experiences among Black–White multiracials, the depiction of Asian multiracials as White-leaning—though based on limited empirical evidence—continues to be prominent, revealing the tendency to view Asian–White individuals through a “White racial frame.” The racial identifications and experiences of Asian–White multiracials are far more complex than such a view suggests. We argue for the need to advance studies on Asian mixed-race people to accurately capture their racial positioning within a system of White supremacy, including the diversity of their identifications, political views, and racialized experiences.
Time-dependent frequency trajectories are an inherent feature of many behaviorally relevant sounds, such as species-specific vocalizations. Dynamic frequency trajectories, even in short sounds, often ...convey meaningful information, which may be used to differentiate sound categories. However, it is not clear what and where neural responses in the auditory cortical pathway are critical for conveying information about behaviorally relevant frequency trajectories, and how these responses change with experience. Here, we uncover tuning to subtle variations in frequency trajectories in auditory cortex of female mice. We found that auditory cortical responses could be modulated by variations in a pure tone trajectory as small as 1/24th of an octave, comparable to what has been reported in primates. In particular, late spiking after the end of a sound stimulus was more often sensitive to the sound's subtle frequency variation compared to spiking during the sound. Such "Off" responses in the adult A2, but not those in core auditory cortex, were plastic in a way that may enhance the representation of a newly acquired, behaviorally relevant sound category. We illustrate this with the maternal mouse paradigm for natural vocalization learning. By using an ethologically inspired paradigm to drive auditory responses in higher-order neurons, our results demonstrate that mouse auditory cortex can track fine frequency changes, which allows A2 Off responses in particular to better respond to pitch trajectories that distinguish behaviorally relevant, natural sound categories.
A whistle's pitch conveys meaning to its listener, as when dogs learn that distinct pitch trajectories whistled by their owner differentiate specific commands. Many species use pitch trajectories in their own vocalizations to distinguish sound categories, such as in human languages like Mandarin. How and where auditory neural activity encodes these pitch trajectories as their meaning is learned is not well understood, especially for short duration sounds. We studied this in mice, where infants use ultrasonic whistles to communicate to adults. We found that late neural firing after a sound ends can be tuned to how the pitch changes in time, and that this response in a secondary auditory cortical field changes with experience to acquire a pitch change's meaning.
B7-H3, a cell surface transmembrane glycoprotein, was assessed for its functional and prognostic role in cutaneous melanoma progression. B7-H3 expression in melanoma cells was shown to be related to ...specific downstream signal transduction events as well as associated with functional epigenetic activity. B7-H3 expression and prognostic utility were shown by reverse transcription and real-time PCR and immunohistochemistry analysis on individual melanoma specimens and then verified in clinically annotated melanoma stage III and stage IV metastasis tissue microarrays in a double-blind study. B7-H3 messenger RNA expression was shown to be significantly increased with stage of melanoma (P<0.0001) and significantly associated with melanoma-specific survival in both stage III (P<0.0001) and stage IV (P<0.012) melanoma patients. B7-H3 expression was related to migration and invasion; overexpression of B7-H3 increased migration and invasion, whereas knockdown of B7-H3 reduced cell migration and invasion. MiR-29c expression was shown to inversely regulate B7-H3 expression. Furthermore, we demonstrated that melanoma B7-H3 expression was correlated to phosphorylated signal transducer and activator of transcription-3 activity level in melanoma tissues and cell lines. These studies demonstrate that B7-H3 is a significant factor in melanoma progression and events of metastasis.
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