La morphogenèse du pied de l'embryon de poulet étudiée à l'aide de malformations provoquées par le vert Janus

Development ◽  
1976 ◽  
Vol 35 (3) ◽  
pp. 649-665
Author(s):  
Marie-Paule Pautou

Morphogenesis of the chick embryo foot as studied by Janus green B-induced malformations Janus green was injected into the amnioticsac of 6·5-day-old chick embryos at a single dose of 8·5 or 15 μg; the dye causes respectively 55 and 82 % malformations of the feet. Toes are affected by partial or total soft tissue syndactyly, hypophalangy and infrequently by hyperphalangy. Lateral toes are more severely and more frequently affected by syndactyly and hypophalangy than medium ones. Hyperphalangy is found exclusively in toes I and II and causes the formation of one excess phalanx at most Syndactylous toes are joined by an overdeveloped digital membrane. Hypophalangic toes have a truncated (non-pointed) distaltip. Two phalanges are lacking at most. These malformations are due to two distinct phases of the Janus green action. The first one, which is early and fast, inhibits interdigital programmed cell death, causing in term the non-regression of the inter digital membranes and thus syndactyly. The second one, which is late and slow, blocks the apical growth; this leads to hypophalangy.

2021 ◽  
Vol 9 (2) ◽  
pp. e001696
Author(s):  
Yi Que ◽  
Xiao-Long Zhang ◽  
Ze-Xian Liu ◽  
Jing-Jing Zhao ◽  
Qiu-Zhong Pan ◽  
...  

BackgroundThe advent of immune checkpoint therapy has been a tremendous advance in cancer treatment. However, the responses are still insufficient in patients with soft tissue sarcoma (STS). We aimed to identify rational combinations to increase the response to immune checkpoint therapy and improve survival.MethodsWhole-exome sequencing (WES) was performed in 11 patients with liposarcoma. Somatic copy number alterations (SCNAs) were analyzed at the gene level to identify obvious amplification patterns in drug-target genes. The expression and prognostic value of class I histone deacetylases (HDACs) was evaluated in 49 patients with sarcoma in our center and confirmed in 263 sarcoma samples from The Tumor Cancer Genome Atlas (TCGA) database. Q-PCR, flow cytometry and RNA-seq were performed to determine the correlations between class I HDACs, chidamide and PD-L1 in vitro and in vivo. The efficacy of combining chidamide with PD-1 blockade was explored in an immunocompetent murine model and a small cohort of patients with advanced sarcoma. Western blot, ChIP assay and dual luciferase assessment were applied in the mechanistic study.ResultsThe HDAC gene family was frequently amplified in STS. SCNAs in the HDAC gene family were extensively amplified in 8 of 11 (73%) patients with liposarcoma, based on a drug-target gene set, and we verified amplification in 76.65% (197/257) of cases by analyzing TCGA sarcoma cohort. Class I HDAC expression is associated with a poor prognosis for patients with STS, and its inhibition is responsible for promoting apoptosis and upregulating of programmed cell death ligand 1 (PD-L1). The HDAC class I inhibitor chidamide significantly increases PD-L1 expression, increased the infiltration of CD8+ T cells and reduced the number of MDSCs in the tumor microenvironment. The combination of chidamide with an anti-PD-1 antibody significantly promotes tumor regression and improves survival in a murine model. Moreover, chidamide combined with the anti-PD-1 antibody toripalimab is effective in patients with advanced and metastatic sarcoma, and the side effects are tolerable. Mechanistically, chidamide increases histone acetylation at the PD-L1 gene through the activation of the transcriptional factor STAT1.ConclusionsThe combination of chidamide and anti-programmed cell death 1 (PD-1) therapy represents a potentially important strategy for STS.


2011 ◽  
Vol 55 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Anna Gibson ◽  
Neil Robinson ◽  
Andrea Streit ◽  
Guojun Sheng ◽  
Claudio D. Stern

1999 ◽  
Vol 200 (5) ◽  
pp. 509-519 ◽  
Author(s):  
A. Lawson ◽  
Gary C. Schoenwolf ◽  
Marjorie A. England ◽  
Frederick K. Addai ◽  
Rexford S. Ahima

Cancer ◽  
2017 ◽  
Vol 123 (17) ◽  
pp. 3291-3304 ◽  
Author(s):  
Seth M. Pollack ◽  
Qianchuan He ◽  
Jennifer H. Yearley ◽  
Ryan Emerson ◽  
Marissa Vignali ◽  
...  

1995 ◽  
Vol 58 (2) ◽  
pp. 243-248 ◽  
Author(s):  
Noriko TAKASHITA ◽  
Shunsaku HOMMA ◽  
Rocco J. ROTTELLO ◽  
Pierre-Alan FERNANDEZ ◽  
Junying YUAN ◽  
...  

1999 ◽  
Vol 38 (2) ◽  
pp. 171-190 ◽  
Author(s):  
Vict�ria Ayala ◽  
C�lia Casas ◽  
Joan Ribera ◽  
Jordi Calder� ◽  
Ronald W. Oppenheim ◽  
...  

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