scholarly journals Investigating the Role of Beta-Catenin in Sex Determination.

2008 ◽  
Vol 78 (Suppl_1) ◽  
pp. 189-190 ◽  
Author(s):  
Danielle M. Maatouk ◽  
Leo DiNapoli ◽  
Makoto M. Taketo ◽  
Blanche Capel
Neuroscience ◽  
2017 ◽  
Vol 357 ◽  
pp. 285-294 ◽  
Author(s):  
Nachshon Korem ◽  
Rachel Lange ◽  
Cecilia J. Hillard ◽  
Irit Akirav

Author(s):  
Elena Fountzilas ◽  
Razelle Kurzrock ◽  
Henry Hiep Vo ◽  
Apostolia-Maria Tsimberidou

Abstract The development of checkpoint blockade immunotherapy has transformed the medical oncology armamentarium. But, despite its favorable impact on clinical outcomes, immunotherapy benefits only a subset of patients, and a substantial proportion of these individuals eventually manifest resistance. Serious immune-related adverse events and hyper-progression have also been reported. It is therefore essential to understand the molecular mechanisms and identify the drivers of therapeutic response and resistance. In this review, we provide an overview of the current and emerging clinically relevant genomic biomarkers implicated in checkpoint blockade outcome. U.S. Food and Drug Administration–approved molecular biomarkers of immunotherapy response include mismatch repair deficiency/microsatellite instability and tumor mutational burden ≥10 mutations/megabase. Investigational genomic-associated biomarkers for immunotherapy response include alterations of the following genes/associated pathways: chromatin remodeling (ARID1A, PBRM1, SMARCA4, SMARCB1, BAP1), major histocompatibility complex, specific (e.g., ultraviolet, APOBEC) mutational signatures, T-cell receptor repertoire, PDL1, POLE/POLD1, and neo-antigens produced by the mutanome; those potentially associated with resistance include β2-microglobulin, EGFR, Keap1, JAK1/JAK2/interferon-gamma signaling, MDM2, PTEN, STK11, and Wnt/Beta-catenin pathway alterations. Prospective clinical trials are needed to assess the role of a composite of these biomarkers in order to optimize the implementation of precision immunotherapy in patient care.


Development ◽  
1995 ◽  
Vol 121 (1) ◽  
pp. 99-111 ◽  
Author(s):  
M.A. Pultz ◽  
B.S. Baker

The hermaphrodite (her) locus has both maternal and zygotic functions required for normal female development in Drosophila. Maternal her function is needed for the viability of female offspring, while zygotic her function is needed for female sexual differentiation. Here we focus on understanding how her fits into the sex determination regulatory hierarchy. Maternal her function is needed early in the hierarchy: genetic interactions of her with the sisterless genes (sis-a and sis-b), with function-specific Sex-lethal (Sxl) alleles and with the constitutive allele SxlM#1 suggest that maternal her function is needed for Sxl initiation. When mothers are defective for her function, their daughters fail to activate a reporter gene for the Sxl early promoter and are deficient in Sxl protein expression. Dosage compensation is misregulated in the moribund daughters: some salivary gland cells show binding of the maleless (mle) dosage compensation regulatory protein to the X chromosome, a binding pattern normally seen only in males. Thus maternal her function is needed early in the hierarchy as a positive regulator of Sxl, and the maternal effects of her on female viability probably reflect Sxl's role in regulating dosage compensation. In contrast to her's maternal function, her's zygotic function in sex determination acts at the end of the hierarchy. This zygotic effect is not rescued by constitutive Sxl expression, nor by constitutive transformer (tra) expression. Moreover, the expression of doublesex (dsx) transcripts appears normal in her mutant females. We conclude that the maternal and zygotic functions of her are needed at two distinctly different levels of the sex determination regulatory hierarchy.


1995 ◽  
Vol 103 (suppl 7) ◽  
pp. 73-77 ◽  
Author(s):  
D Crews ◽  
J M Bergeron ◽  
J A McLachlan
Keyword(s):  

Author(s):  
Ayan Kundu ◽  
Anway Sen ◽  
Shouvik Choudhury ◽  
Tapan Kumar Mandal ◽  
Debasish Guha ◽  
...  

Background and aims. Renal cell carcinoma (RCC) seems to be the most aggressive type of genitourinary neoplasm. Down regulation of normal beta-catenin expression contributes to development of RCC, reflecting the role of beta-catenin/Wnt signaling pathway in pathogenesis. This study aims to evaluate the significance of beta-catenin expression and its correlation with the prognostic parameters. Methods. A cross-sectional observational study was carried out in a tertiary care center on 58 RCC cases using variables like histological grade and type, tumor stage, necrosis. Formalin fixed, paraffin-embedded blocks were evaluated for beta-catenin expression by immunohistochemistry using scoring system. Data were analyzed by mean ± SD, χ2 test, Pearson’s correlation test. Results. Membranous score (MS) had a strong negative correlation with tumor stage (r = -0.407, p = 0.044) and grade (r = -0.787, p = <0.001). Mean membranous score difference between low (Stage 1 and 2) vs. high stage (Stage 3 and 4) and low (Grade 1 and 2) vs. high grade (Grade 3 and 4) was statistically significant (p < 0.001). Cytoplasmic score (CS) had positive correlation with tumor stage (r = 0.586; p = 0.002). No significant correlation was evident between cytoplasmic scores and tumor grade, however the mean cytoplasmic score difference between low grade vs. high grade was statistically significant (p < 0.001). Conclusion. Beta-catenin may play a crucial role in the pathogenesis of RCC and has a positive correlation with the biological behavior of this tumor. The important role of beta-catenin as a prognostic parameter and probably a critical evaluator of targeted chemotherapy cannot be overemphasized.


Sign in / Sign up

Export Citation Format

Share Document