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Melanie A. Krook Julie W. Reeser Gabrielle Ernst Hannah Barker Max Wilberding Gary Li Hui-Zi Chen Sameek Roychowdhury 《British journal of cancer》2021,124(5):880
Fibroblast growth factor receptors (FGFRs) are aberrantly activated through single-nucleotide variants, gene fusions and copy number amplifications in 5–10% of all human cancers, although this frequency increases to 10–30% in urothelial carcinoma and intrahepatic cholangiocarcinoma. We begin this review by highlighting the diversity of FGFR genomic alterations identified in human cancers and the current challenges associated with the development of clinical-grade molecular diagnostic tests to accurately detect these alterations in the tissue and blood of patients. The past decade has seen significant advancements in the development of FGFR-targeted therapies, which include selective, non-selective and covalent small-molecule inhibitors, as well as monoclonal antibodies against the receptors. We describe the expanding landscape of anti-FGFR therapies that are being assessed in early phase and randomised controlled clinical trials, such as erdafitinib and pemigatinib, which are approved by the Food and Drug Administration for the treatment of FGFR3-mutated urothelial carcinoma and FGFR2-fusion cholangiocarcinoma, respectively. However, despite initial sensitivity to FGFR inhibition, acquired drug resistance leading to cancer progression develops in most patients. This phenomenon underscores the need to clearly delineate tumour-intrinsic and tumour-extrinsic mechanisms of resistance to facilitate the development of second-generation FGFR inhibitors and novel treatment strategies beyond progression on targeted therapy.Subject terms: Cancer, Cancer 相似文献
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Joachim Fensterle 《Journal der Deutschen Dermatologischen Gesellschaft》2006,4(3):205-216
Many cellular signaling pathways are involved in the development of cancer. Depending on the tumor entity, the nature as well as the mode of activation can differ. Some signaling pathways frequently show changes as all tumor cells have to fulfill some basic requirements such as independence from growth factors or insensitivity against apoptosis. In this review, the possibilities of a tumor to manipulate signaling pathways to reach these goals are exemplified based on an archetypical melanoma cell. In addition, new therapeutic options based on the knowledge of signaling pathways will be discussed. 相似文献
6.
Robert A. Mischkowski Max J. Zinser Alexander C. Kübler Barbara Krug Ulrich Seifert Joachim E. Zller 《Journal of cranio-maxillo-facial surgery》2006,34(8):478-483
BACKGROUND: An augmented reality tool for computer assisted surgery named X-Scope allows visual tracking of real anatomical structures in superposition with volume rendered CT or MRI scans and thus can be used for navigated translocation of bony segments. METHODS: In a feasibility study X-Scope was used in orthognathic surgery to control the translocation of the maxilla after Le Fort I osteotomy within a bimaxillary procedure. The situation achieved was compared with the pre-operative situation by means of cephalometric analysis on lateral and frontal cephalograms. RESULTS: The technique was successfully utilized in 5 patients. Maxillary positioning using X-Scope was accomplished accurately within a range of 1mm. The tool was used in all cases in addition to the usual intra-operative splints. A stand-alone application without conventional control does not yet seem reasonable. CONCLUSION: Augmented reality tools like X-Scope may be helpful for controlling maxillary translocation in orthognathic surgery. The application to other interventions in cranio-maxillofacial surgery such as Le Fort III osteotomy, fronto-orbital advancement, and cranial vault reshaping or repair may also be considered. 相似文献
7.
Joachim Dissemond Andreas Krber Stephan Grabbe 《Journal der Deutschen Dermatologischen Gesellschaft》2006,4(8):627-634
In Germany about 0.7 % of the adult population have a chronic leg ulcer. Although chronic venous insufficiency accounts for at least 80 % of all chronic leg ulcers, knowledge of the relevant differential diagnostic considerations is of crucial importance, in particular for patients who are refractory to therapy. In addition to vascular disease, other causes include neuropathic, metabolic, hematologic and exogenous factors as well as neoplasias, infections, drugs, genetic defects and some primary skin disorders. For the long‐term successful treatment of patients with chronic leg ulcers, it is necessary to identify all relevant factors, in order to enable a pathogenesis‐oriented, interdisciplinary therapeutic approach. 相似文献
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W. Nörenberg Ernst Schöffel Bela Szabo Klaus Starke 《Naunyn-Schmiedeberg's archives of pharmacology》1997,356(2):159-165
The aim of the study was to subclassify the soma-dendritic α2-autoreceptors in the locus coeruleus (LC) of the rat by means of antagonists. To this end, the frequency of spontaneous action
potentials was recorded extracellularly from single LC neurones in brain slices. The neurones fired spontaneously at an average
rate of 1 Hz. The selective α2-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) and noradrenaline decreased the action potential
discharge with IC50 values of 5 and 510 nM, respectively. The concentration-inhibition curves of UK 14,304 and noradrenaline were shifted to the
right by phentolamine (0.15 μM) and rauwolscine (0.15 μM) but not by prazosin (1 μM). Apparent K
d values of phentolamine were 17 nM (against UK 14,304) and 20 nM (against noradrenaline). Apparent K
d values of rauwolscine were 47 nM (against UK 14,304) and 70 nM (against noradrenaline). (+)-Oxaprotiline (1 μM) suppressed
the firing of the neurones within 10 to 33 min. In the continued presence of oxaprotiline, phentolamine and rauwolscine restored
firing with EC50 values of 120 and 250 nM, respectively. Prazosin (1 μM) again was ineffective. All three antagonist affinity estimates –
against UK 14,304, exogenous noradrenaline and endogenous noradrenaline (that accumulates in the extracellular space in the
presence of oxaprotiline) – yield an affinity order phentolamine > rauwolscine >> prazosin, prazosin being ineffective even
at a concentration of 1 μM. These findings identify the soma-dendritic α2-autoreceptors of the LC as the rat variant of the α2A/D-adrenoceptor, i.e. α2D. Not only presynaptic but also soma-dendritic α2-autoreceptors may at least predominantly be α2A/D throughout the nervous system.
Received: 3 March 1997 / Accepted: 21 April 1997 相似文献
10.
Frank Marusch Andreas Koch Uwe Schmidt Hubertus Wenisch Michael Ernst Thomas Manger Stefanie Wolff Matthias Pross Jörg Tautenhahn Ingo Gastinger Hans Lippert 《Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie》2002,387(2):94-100
BACKGROUND: The problems associated with rectal surgery are frequently discussed with no reference being made to the distance of the tumor from the anal verge. This study examined the effect of the location of the tumor on early postoperative results. PATIENTS AND METHODS: This was a multicenter study involving 75 German hospitals and 3756 patients, of whom 1463 had rectal carcinoma. On the basis of the location of the tumor (distance from the anal verge), four groups were distinguished: <4, 4-7.9, 8-11.9, and 12-16 cm. RESULTS: Resection and abdominoperineal resection rates and the incidence of postoperative complications depended on the location of the tumor. Significantly higher resection rates and fewer specific complications, and a significant reduction in overall postoperative morbidity were found with tumor locations more than 8 cm from the anal verge. The highest anastomotic leak rate was observed with anastomoses less than 7 cm from the anal verge. The logistic regression showed that the distance of the tumor from the anal verge is an independent variable for the development of an anastomotic leak. CONCLUSIONS: Early results are greatly affected by the location of the rectal carcinoma. This applies to both abdominoperineal resection rates and specific postoperative complications, such as anastomotic leak rate and operation morbidity in general. 相似文献