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Case 2.11
Published in Monica Fawzy, Plastic Surgery Vivas for the FRCS(Plast), 2023
This patient has Pfeiffer syndrome. Please tell me more about thisThis is an autosomal dominant syndrome with FGFR2 mutation on chromosome 2 with an incidence of 1:100,000 live births. A minority of patients with less severe phenotype have FGFR1 mutation.It manifests asa turribrachycephaly with bicoronal synostoses, oras a Kleeblattschadel or cloverleaf with numerous synostoses, in 25%.Intracranial anomalies include hydrocephalus and Chiari malformation.Orbital anomalies include exorbitism, hypertelorism, downslanting palpebral fissures, and strabismus.Midface anomalies include midface hypoplasia with a low nasal bridge.Classically, they have broad thumbs and halluces.
Hormone Receptors and Endocrine Therapy in Breast Cancer
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Sherry X. Yang, Nancy E. Davidson
Though rare in primary breast cancers, the gain-of-function mutations in the ESR1 have been found in about 20–30% of metastatic ER+ breast cancer after endocrine treatment [107]. The mutations are clustered within the ligand-binding domain of the gene and lead to a ligand-independent ER activity. The latter promotes tumor growth and plays a role in the acquired resistance to endocrine therapy in the metastatic disease. Amplification of fibroblast growth factor receptor 1 (FGFR1) occurs in approximately 10% of breast cancers [108]. FGFR1 amplified breast cancer cells were resistant to Tamoxifen in vitro, and may be correlated to a poorer response to endocrine therapy. FGFR1 receptor overexpression activates the PI3K pathway, which leads to the resistance to hormone therapy. CCND1 amplification occurs in 29% of luminal A, and 58% of luminal B tumors, which predicted poor outcome in postmenopausal breast cancer patients treated with anastrozole or tamoxifen [109, 110]. Amplification on 11q13 and 8p11, and other driver alterations were associated with an increased risk of distant recurrence in subsets of postmenopausal patients with ER-positive, HER2-negative early breast cancer receiving endocrine therapy [111].
The respiratory system
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
These are commonly central tumours, in main or segmental bronchi, and they often present earlier than other types of carcinoma because of obstructive symptoms. However, in recent years they have increasingly been seen in the periphery of the lung, which may reflect changing smoking behaviour. The tumour is solid and greyish/white, and may show cavitation. These tumours arise from the bronchial epithelium through a process of squamous metaplasia through dysplasia to squamous carcinoma in situ, and these changes may be seen adjacent to the invasive tumour. The tumour is composed of large cells with squamous differentiation characterized by keratinization and/or intercellular bridges (Figure 8.31). Squamous cell carcinoma shows a diverse range of mutations including losses in chromosomes 3p, 9p, and 17p, corresponding to losses of tumour suppressor genes including CDKN2A and TP53, which occur early in tumour evolution. In addition, amplification of the fibroblast growth factor receptor gene, FGFR1, is seen in many cases and may be a target for therapy.
FGFR2 modulates the Akt/Nrf2/ARE signaling pathway to improve angiotensin II-induced hypertension-related endothelial dysfunction
Published in Clinical and Experimental Hypertension, 2023
Kun Jiao, Ping Su, Yongling Li
Fibroblast growth factor receptor (FGFR)2 is a member of the receptor tyrosine kinase subfamily, which also includes FGFR1, FGFR3 and FGFR4 (3). Serum FGFR2 was significantly reduced in fracture patients, and FGFR2 could regulate osteoblast viability and apoptosis (4). FGFR2 deletion led to defective vesical urethral epithelial regeneration after cyclophosphamide injury (5). FGFR2 expression was downregulated in caerulein-induced pancreatic cells and FGFR2 overexpression decreased the caerulein-induced inflammatory injury in pancreatic cells (6). FGFR2 deletion in tubular cells exacerbated acute renal dysfunction and tubular cell apoptosis induced by ischemia/reperfusion or cisplatin (7). It can be seen from the above that the decrease of FGFR2 is harmful to the body, and the increase of FGFR2 expression can reverse the body injury. Peripheral blood microarray sequencing in patients with essential hypertension and volunteers with normal blood pressure in the GSE24752 dataset showed down-regulated FGFR2 expression in hypertension patients (8). However, its role in hypertension has not been reported.
The effect of two concurrent exercise modalities on serum concentrations of FGF21, irisin, follistatin, and myostatin in men with type 2 diabetes mellitus
Published in Archives of Physiology and Biochemistry, 2023
Morteza Motahari Rad, Nahid Bijeh, Seyyed Reza Attarzadeh Hosseini, Aliakbar Raouf Saeb
As for further explanation, FGF21 induced by muscle-contraction seems to coordinate multi-organ crosstalk for preserving metabolic homeostasis (Geng et al.2019). In our study, the concentrations of FGF21 did not change significantly following the CT. In the same line, Banitalebi et al. (2019) reported that ten weeks of CT in T2DM patients did not show a significant difference in the FGF21 serum concentrations (Banitalebi et al.2019), whereas in T2DM patients it was determined that circulating concentrations of FGF21 increased while their receptors decreased, which led to the reduction of FGF21 sensitivity (Geng et al.2019, Garneau et al.2020). Geng et al. (2019) illustrated that AT increased the expression of FGF receptor-1 (FGFR1) and liver kinase B1 (LKB1) without changing FGF21 concentrations via PPAR-γ transcriptional activation in the adipose tissue from rats (Geng et al.2019). In fact, CT probably sensitises FGF21 actions without changing the concentrations of FGF21 in T2DM patients; however, the current study could not provide a definite answer to the effects of FGF21 sensitivity through the 12 weeks of CT.
Immunomodulation via FGFR inhibition augments FGFR1 targeting T-cell based antitumor immunotherapy for head and neck squamous cell carcinoma
Published in OncoImmunology, 2022
Michihisa Kono, Hiroki Komatsuda, Hidekiyo Yamaki, Takumi Kumai, Ryusuke Hayashi, Risa Wakisaka, Toshihiro Nagato, Takayuki Ohkuri, Akemi Kosaka, Kenzo Ohara, Kan Kishibe, Miki Takahara, Akihiro Katada, Tatsuya Hayashi, Hiroya Kobayashi, Yasuaki Harabuchi
In this study, we elucidated two aspects of FGFR1 in cancer immunology: as an immune adjuvant and as a target antigen of a peptide vaccine. To the best of our knowledge, there have been no reports elucidating the antitumor T cell response elicited by FGFR1-derived peptides, and only a few studies have investigated the immunomodulatory effects of FGFR1 inhibition. According to the Human Protein Atlas database and previous studies, overexpression of FGFR1 occurs in more than 70% of HNSCC cases.23,24 The expression of FGFR1 is related to poor prognosis in HNSCC,25,26 especially in HPV-negative HNSCC, but not in HPV-positive HNSCC.24,27 Because HPV-negative HNSCC exhibits poor response to standard therapies, developing novel treatments targeting FGFR1 could be a potential approach to treat patients with HNSCC. FGFR1 amplification is associated with poor prognosis in most types of cancer, such as melanoma, lung cancer, pancreatic cancer, and glioblastoma.28–31 Activation of FGFR1 leads to tumor development through its downstream signaling pathways: the Ras-dependent MAPK, PI3K/AKT, and JAK/STAT pathways.7 As these networks contribute to aggressive tumor behavior by activating tumor cell proliferation, survival, differentiation, and migration,32 the development of FGFR1-targeting therapy would be beneficial for patients with aggressive tumors.