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Urothelial and Urethral Cancer
Published in Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple, Basic Urological Sciences, 2021
Ibrahim Jubber, Karl H. Pang, James W.F. Catto
Luminal papillaryProminent FGFR3 mutation.Other highly expressed genes: UPK2, UPK1A, FOXA1, GATA3, PPARG.Papillary architecture.Low likelihood of response to neoadjuvant chemotherapy (NAC).Tyrosine Kinase inhibitors of FGFR3 may be an effective treatment approach.
Breast Surgery
Published in Tjun Tang, Elizabeth O'Riordan, Stewart Walsh, Cracking the Intercollegiate General Surgery FRCS Viva, 2020
Gaural Patel, Lucy Kate Satherley, Animesh JK Patel, Georgina SA Phillips
What are the specific features of invasive lobular breast cancer?Small round tumour cells growing in a single-file patternMore difficult to detect by standard imaging techniques (require MRI)Frequent late recurrences and worse long-term survivalHigher immune activityIncreased metastases to ovary and GI tract, fewer metastases to visceral organsLower response rates to neoadjuvant chemotherapy and tamoxifenLack of E-cadherin (CDH1) protein expressionMore likely to be ER+ and PR+ and less likely to be HER2+Lower Ki67 positivityHigher frequency of HER2, HER3, PIK3CA and FOXA1 mutations and PTEN loss23
Mouse Knockout Models of Biliary Epithelial Cell Formation and Disease
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
Smads are intracellular mediators of TGF-beta that are conserved through evolution. Recent genetic using combinatorial genetics have shown the key roles of Smad2 and Smad4 in gastrulation as well as endoderm formation and liver development.4 Similarly transcription factors Sox 17 (an Sry-related HMG box factor), Mixer (a homeobox protein) and Casanova have been shown to be key determinants of endoderm in Xenopus and zebrafish, with mammalian Sox 17 being crucial for gut endoderm.7 All are expressed in the fetal, adult liver, and other endoderm derived tissues and the fox proteins regulate virtually all liver-specific genes, as well as genes in the lung and the pancreas. 8,9Foxa2 (formerly Hnf3b) is expressed during gastrulation (6.5 days of embryonic gestation in the mouse; E6.5) in the primitive streak (an endoderm progenitor) and in the node (an endoderm and notochord progenitor, Foxa1 (Ηnf3α) expression initiates in the gut endoderm at E7- E8, before organogenesis, whereas Foxa3 (Hnf3c) expression begins in the gut endoderm at E8-E9 but is restricted to the midgut and hindgut regions.10,11 Homozygous mutants for Foxa2 result in embryonic lethality shortly after gastrulation, with defects in the primitive streak, node and notochord that impair neural tube development, and in foregut morphogenesis. 12–15 Homozygous mutation in Foxal leads to impaired pancreatic glucagon expression and consequent postnatal death, whereas homozygous mutation in Foxal appear normal, yet have a decrease in the transcription levels of a number of liver genes. These are seen in Figure 1.
FOXO1 and PAX5 Rearrangement in Alveolar Rhabdomyosarcoma in Saudi Pediatric Patients
Published in Fetal and Pediatric Pathology, 2023
ARMS is an aggressive pediatric malignancy of striated muscle characterized in 60% of cases by FOXO1::PAX3 fusion transcript [1,25]. Human Forkhead-box (FOX) gene family consists of at least 43 members [25]. Several pathogenesis and tumorigenesis were attributed to the deregulation of FOX family genes. FOXA1 gene is amplified and overexpressed in esophageal and lung cancer [25]. The upregulation of FOXM1 gene in pancreatic carcinoma was reported to the transcriptional regulation by Sonic Hedgehog pathway [26,27]. FOXO1 gene is fused to PAX3 or PAX7 genes in rhabdomyosarcoma. ARMS cases show whole-chromosome copy number changes, notably gain of chromosome 8 with associated high levels of expression of genes from this chromosome [16,28].
Silencing of long noncoding RNA H19 alleviates pulmonary injury, inflammation, and fibrosis of acute respiratory distress syndrome through regulating the microRNA-423-5p/FOXA1 axis
Published in Experimental Lung Research, 2021
Xianyu Mu, Hongrong Wang, Haiyong Li
The regulatory function of miRNAs in ARDS is directly related to its target genes. For example, miR-200c-3p promotes the apoptosis of A549 cells in ARDS through down-regulating ACE2.24 MiR-494 accelerates lung injury in rats with sepsis-associated ARDS through down-regulating NQO1.25 Silencing of miR-204 aggravates LPS-induced ARDS in mice by up-regulating IRF2 17. FOXA1 is a member of the winged-helix family of transcription factors, which has been reported to promote pulmonary epithelial cell apoptosis in ALI.26 Wei et al. have reported that knockdown of MALAT1 alleviates LPS-induced injury in A549 cells by targeting the miR-17-5p/FOXA1 axis.27 Xu et al. have shown that miR-17 inhibition up-regulates FOXA1 in LPS-induced ALI mice and in LPS-induced type II epithelial cells.28 However, the regulatory mechanism of H19/miR-423-5p/FOXA1 axis on ARDS is still unclear.
Protein biomarkers for subtyping breast cancer and implications for future research
Published in Expert Review of Proteomics, 2018
Claudius Mueller, Amanda Haymond, Justin B. Davis, Alexa Williams, Virginia Espina
Emerging biomarkers have limited validation due to evaluation in small patient cohorts. However, emerging biomarkers may be extremely useful in research settings for deciphering drug sensitivity and resistance, or developing additional clinical disease monitors and treatment monitors. Several studies have recognized the forkhead box transcription factors as potential predictive biomarkers for overcoming trastuzumab resistance or for the need for adjuvant chemotherapy [111,112,113,177]. FOXA1 has been positively correlated with good prognosis in ER/PR+ breast cancer and negatively correlated with Ki-67 and nuclear grade [111,113]. GATA-3, transacting T-cell-specific transcription factor, has also been found to be associated with luminal A and luminal B subtypes [114]. GATA-3 correlated with FOXA1 but FOXA1 remained the better independent marker for prognosis and prediction for adjuvant chemotherapy [111,113].