China
Africa
Explore chapters and articles related to this topic
Endocrine and Neuroendocrine Tumors
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Natasha Shrikrishnapalasuriyar, P.N. Plowman, Márta Korbonits, Ashley B. Grossman
RET is a transmembrane receptor protein-tyrosine kinase that is required for the development of the nervous system/neural crest and several other tissues. The mechanism of activation of RET by its glial-cell derived neurotrophic factor (GDNF) ligands requires additional GDNF family receptor-α (GFRα) co-receptors (GFRα1/2/3/4). RET point mutations have been reported in multiple endocrine neoplasia (MEN2A, MEN2B) and medullary thyroid carcinoma. RET fusion proteins have been reported in papillary thyroid and non-small cell lung adenocarcinomas. There has been much recent interest and clinical benefit from the use of the RET inhibitors in the therapy of metastatic medullary thyroid cancer. Vandetanib and cabozantinib have been licensed and are of proven efficacy; recently, a more potent agent, Blue-667, has become available and looks more promising still. This last drug has activity in the brain (of more importance in the RET-driven lung cancers than medullary carcinoma of thyroid). Side-effects such as hypertension, ECG changes, and blood test abnormalities are usually minor but close monitoring is required—as for all cancer patients on tyrosine kinase inhibitors.
Endothelial Cell Signaling During Wound Healing
Published in John J. Lemasters, Constance Oliver, Cell Biology of Trauma, 2020
The experiments described above were designed to define the role and mechanisms of tyrosine phosphorylation events during endothelial cell wound healing. We have employed specific tyrosine kinase inhibitors with two different mechanisms of action to probe these issues. We have previously demonstrated herbimycin A inhibition of focal adhesion formation, and stress fiber assembly in REF52, NIH 3T3 and Balb/c 3T3 cells68,69 in a pattern similar to that seen in tyrphostin-treated HUVEC, VEC, and REF52 (see Figures 6 and 7, above). The fact that both herbimycin A and tyrphostins also inhibited FAK activity and endothelial cell wound healing42 suggests that it is the inhibition of tyrosine kinase activity, rather than any other effect of these agents, that accounts for these observations. These agents were chosen in part for their specificity. Tyrphostins are competitive tyrosine kinase inhibitors80 that have been shown to have no effect on the activity of serine and threonine kinases.89 Herbimycin A has proven a potent inhibitor of Src-family tyrosine kinases, while it did not alter the activity of other oncogene products including raf, ras, or myc.90 The specificities of these agents contrast with the range of specificity reported for other tyrosine kinase inhibitors such as genistein and erbstatin that also inhibit protein kinases A and C.91,92
Scleroderma and associated complications
Published in Biju Vasudevan, Rajesh Verma, Dermatological Emergencies, 2019
Yasmeen Jabeen Bhat, Safiya Bashir
Interstitial lung disease: Cyclophosphamide in combination with high-dose corticosteroids is effective in early stages [83]. Tyrosine kinase inhibitors such as imatinib offer a promising future option [84]. Hematopoietic stem cell transplant and lung transplant may be considered in rapidly progressive and end-stage lung disease, respectively.
Safety of sunitinib in patients with renal cell carcinoma following nephrectomy
Published in Expert Opinion on Drug Safety, 2020
Luc Heraudet, Charlotte Domblides, Amaury Daste, Félix Lefort, Jean-Christophe Bernhard, Alain Ravaud, Marine Gross-Goupil
Antiangiogenic agents, monoclonal antibody, and tyrosine kinase inhibitors targeting VEGF-R have dramatically improved the prognosis of advanced or metastatic clear cell RCC. Since its approval, sunitinib has been used for RCC for more than 10 years and has been the standard of care in the first-line setting until recently. The importance of AE management, or prevention when feasible, has frequently been reported in the metastatic setting [26]. It has also been demonstrated that the dose intensity determines the efficacy of sunitinib treatment in mRCC patients, suggesting the importance of maintaining a sufficient daily dose and exposure period. The importance of drug management has been widely reported during the last decade [40,41] High inter-subject variability in tyrosine kinase inhibitor exposure may explain the inter-subject variability in toxicity at the same fixed dose. According to the most recent data from the SURTIME and CARMENA trials, the toxicity profile of sunitinib, administered shortly after post-nephrectomy, was similar to those reported during the past decade of use [8,9].
Dipeptidyl peptidase 4 (DPP-4) inhibitors and the risk of lung cancer: current evidence and future directions
Published in Expert Review of Clinical Pharmacology, 2023
Harmanjit Singh, Jatin Sharma, Pallavi Sikarwar, Ashish Kumar Kakkar
A retrospective study done by Miao et al. in 2016 included histological confirmed NSCLC – advanced (n = 228) as well as early stage (n = 73) patients. Among them, 103 patients were on antihypertensive drugs, from which 52 patients were on ACE inhibitors and ARBs and 51 on other antihypertensive drugs. The study demonstrated that there was a significant difference in progression free survival between the ACE inhibitor/ARB group and the non-ACE inhibitor/ARB group after receiving first line therapy [58]. Similar differences were noted in patients who received tyrosine kinase inhibitors. Positive effects on progression free or overall survival were noted with ACE inhibitor/ARB usage irrespective of the fact whether the lung cancer was in early or late stage.
Repurposed anti-cancer drugs: the future for anti-infective therapy?
Published in Expert Review of Anti-infective Therapy, 2020
Héctor Quezada, Mariano Martínez-Vázquez, Esaú López-Jácome, Bertha González-Pedrajo, Ángel Andrade, Ana María Fernández-Presas, Arturo Tovar-García, Rodolfo García-Contreras
Cancer chemotherapy began in 1942 when based on mustard gas the first cytotoxic compounds used for therapeutic purposes were synthesized and evaluated [4], and then many compounds with different targets were developed. Antimetabolites are structurally similar to essential metabolites, but the body cannot use them. Some common classes of antimetabolites are folate antagonists (methotrexate) [5], purine antagonists (6-mercaptopurine) [6], and pyrimidine antagonists (5-fluorouracil) [7]. Some natural products have been also used with success, such as the vinca alkaloids and taxol [8,9]. In 1978 the FDA approved cisplatin, a DNA alkylating agent, to treat ovarian cancer. Over time, cisplatin became a first-line drug for the treatment of several cancers; nowadays it is known that in addition to its effect on DNA, it also generates reactive oxygen species, increasing its cytotoxicity [10]. From 2001 to 2004, the molecularly targeted therapy began. This fact indicated a paradigm shift in the synthesis of anti-cancer drugs since it was sought to inhibit overexpressed enzymes in cancerous processes. For example, imatinib is the first tyrosine kinase inhibitor available for clinical use. Its main action is to selectively block cell proliferation and induce apoptosis in cells that express the Philadelphia chromosome and house the Bcr-Abl tyrosine kinase, a cause of chronic myeloid leukemia. Recently, substances derived from living organisms, or laboratory-produced versions of such substances have been used to treat cancer. This therapy is known as biological therapy [11]. Among the biological therapies are those collectively known as ‘immunotherapy’ [12].