China
Africa
Explore chapters and articles related to this topic
Regulation of the Pituitary Gland by Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
The glycoprotein hormone alpha subunit (αGSU) is the first pituitary hormone gene expressed during embryonic development, at mouse E10.5 [43]. Thyrotrophs are derived from two different populations. The first appears in the rostral tip of the developing pituitary by E12. This population is transient and is independent of Pit1 expression. The second arises by E15.5 and is PIT1-dependent. This population corresponds to the adult thyrotrophs, indicating that Pit1 is important for transactivating TSHβ, and for maintaining the cellular lineage. Thyrotroph embryonic factor (Tef) is expressed exclusively in the rostral portion of the developing pituitary, where the thyrotrophic precursors are located. Tef transactivates the TSHβ promoter, with Pitx1 and Pitx2 also contributing to thyrotroph differentiation. In humans, the fetal thyroid gland reaches maturity by gestational week 11–12, close to the end of the first trimester and begins to secrete thyroid hormones by about gestational week 16. During this period, an adequate supply of maternal thyroid hormones must be sustained to ensure normal neurological development.
Epidemiology of clubfoot
Published in R. L. Mittal, Clubfoot, 2018
Alvarado et al.96 screened cases of familial isolated clubfoot to find any genetic etiology and found that microduplication of chromosome 17q23.1q23.2 is a common cause and provides strong evidence linking it to clubfoot etiology. A recurrent chromosome 17q23.1q23.2 microduplication was identified in 3 of 66 probands with familial isolated clubfoot, which is significant. Osseous abnormalities in the foot bones were also present. The authors also discovered in one of the isolated clubfoot probands a microdeletion at that location. They further found that chromosome 17q23.1q23.2 contains the T-box transcription factor PITX1-TBX4, previously implicated in clubfoot etiology. This chromosomal abnormality therefore appears to be strong evidence in familial isolated clubfoot etiology resulting in abnormal early lower-limb development.
Articular Cartilage Development
Published in Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi, Articular Cartilage, 2017
Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi
Initiation of the forelimbs and hindlimbs is controlled by expression of different T-box (Tbx) DNA binding domain-containing transcription factors. Based on initial overexpression models, Tbx4 and 5 were thought to regulate forelimb and hindlimb discrimination, as the expression of tbx genes 5 and 4 differs, respectively, between forelimbs and hindlimbs. However, these have been reclassed as limb initiators, not as determiners of forelimb or hindlimb (Minguillon et al. 2005). Instead, induction of morphology specific to the hindlimb has been supported as a role for Pitx1 (DeLaurier et al. 2006). Interestingly, although the molecular components and steps of limb bud initiation are similar between eutherian (placental) and marsupial mammals, the forelimb initiation and subsequent development occur at a much earlier developmental stage, enabling ex utero migration of the joey to the pouch (Keyte and Smith 2010). A rough timeline of limb and cartilage formation is depicted in Figure 2.8.
Searching for DNA methylation in patients triple-negative breast cancer: a liquid biopsy approach
Published in Expert Review of Molecular Diagnostics, 2023
Irsa Shoukat, Christopher R. Mueller
Tumor-specific DNA methylation events can also be detected in cfDNA obtained by liquid biopsies[80–84]. In breast cancer, several groups have shown the potential for cancer detection and prognosis based on gene methylation. For instance, Gobel et al. identified methylation of two promising genes, PITX2 and RASSF1A, from peripheral blood-plasma (PB-P) and bone marrow plasma (BM-P) of primary breast cancer patients (n = 428) as promising prognostic markers[82]. The study identified that methylation of both PITX2 and RASSF1A in PB-P indicated poor OS and distance disease-free survival. [(PITX1: P = 0.001 and P = 0.023) (RASSF1A: P = 0.001 and P = 0.004[82]. In BM-P, methylation of RASSF1A also showed significant prognostic potential (P = 0.016). Interestingly, methylation of RASSF1A was observed in other studies. Using serum for detection of localized, early-stage breast cancer, the methylation status of a three-gene panel including genes ITIH5, DKK3, and RASSF1A was characterized as being valuable biomarkers[83]. Furthermore, monitoring of RASSF1A methylation in the serum of breast cancer patients that had locally advanced breast cancer and were undergoing neo-adjuvant therapy showed prognostic potential for timely assessment of treatment response and drug toxicity[81]. RASSF1A and NEUROD1 were shown to also be useful for monitoring the efficacy of adjuvant therapy in breast cancer patients[85–87]. Nevertheless, these assays would face challenges in showing good clinical utility because they are not malignancy-specific as RASSF1A methylation was also observed in patients with benign breast lesions as well as healthy controls[82]. Methylation of other biomarkers including p16INK4A, CDH1, DAPK11, HIC1, RARB, CDH13, ESR1, GSTP1, have also been evaluated in serum either alone or in combination (reviewed in[88]); however, none of them have been incorporated into a clinical laboratory assay and nor have they specifically analyzed TNBC patients. Therefore, there has been a push for the development of additional blood-based markers to provide more robust, reproducible, quantitative, and sensitive assays for breast cancer subtypes. The technical details of the established methylation assays are described in Table 1.