Complications of Intravesical Therapy
Kevin R. Loughlin in Complications of Urologic Surgery and Practice, 2007
Gemcitabine is a pyrimidine antimetabolite, analogous to cytosine arabinoside, with a molecular weight of 300 Da. Its mechanism of action involves incorporation of the pyrimidine base analog into DNA by one of the metabolites [2′, 2′-difluorodeoxycytidine (dFdCTP)], resulting in chain termination (79). In addition, gemcitabine inhibits ribonucleotide reductase, an enzyme necessary for DNA synthesis (80). It was first approved in the United States to treat pancreatic cancer (81) but has since been found to be effective in other tumors such as non-small-cell lung cancer, leiomyosarcoma, and ovarian cancer (82). Phase III clinical trial revealed similar survival rates in patients but reduced toxicity with metastatic urothelial cancer treated with gemcitabine plus cisplatin versus the conventional treatment with methotrexate, vinblastine, doxorubicin, and cisplatin (83).
Caffeine and arousal: a biobehavioral theory of physiological, behavioral, and emotional effects
B.S. Gupta, Uma Gupta in Caffeine and Behavior, 2020
Caffeine is a base analog that acts to antagonize adenosine receptors, thereby affecting a variety of cell populations by partially counteracting many of the effects of adenosine. It acts primarily on the A2a adenosine receptors, elevating energy metabolism in the brain29–31 and producing a 30% decrease in whole-brain CBF, with no regional differences.32 Caffeine also modulates neural activity through its inhibitory effect on ionotropic GABA receptors33 and, like other methylxanthines, acts on serotonin and noradrenaline neurons and affects local dopamine release.31 These actions further explain its stimulating effects, which include activation of major components of the hypothalamic-pituitary-adrenal (HPA) axis response. In particular, caffeine increases adrenocorticotropin (ACTH) release at the pituitary, resulting in elevated Cortisol production.34
HER2-targeted therapy: an emerging strategy in advanced colorectal cancer
Published in Expert Opinion on Investigational Drugs, 2019
Anna La Salvia, Victoria Lopez-Gomez, Rocio Garcia-Carbonero
The clinical management of CRC has notably improved over the last decades determining significant improvements in patients’ survival. However, if not suitable for surgical approach, mCRC is still not curable with available therapy. The combination and sequential administration of chemotherapy (fluoropyrimidines with oxaliplatin or irinotecan) with different biologic agents (antiangiogenics such as bevacizumab, aflibercept, or ramucirumab, and anti-EGFR mAbs such as cetuximab or panitumumab in RAS wild-type tumors) are the mainstay of care in advanced CRC [57]. However, for tumors that have progressed to these therapies, available treatment options are scarce and of limited efficacy. Indeed, both currently approved drugs for molecularly unselected, refractory mCRC, the multi-targeted TKI regorafenib [58] and the thymidine-based nucleic acid analogue TAS-102 [59], induce objective responses in <2% of treated patients, and are associated with a median PFS of about 2 months and a median OS of 6–7 months.
Comparison of efficacy and safety for patients with beyond second line treated metastatic colorectal cancer: a network meta-analysis of randomized controlled trials
Published in Journal of Chemotherapy, 2020
Meihui Cao, Mingyi Zhou, Jingdong Zhang
Regorafenib is an oral multikinase inhibitor that blocks kinases involved in angiogenesis (VEGFR1-3 and TIE2), oncogenesis (c-kit, RET, RAF-1, wild-type BRAF and BRAFV600E) and the tumor microenvironment (PDGFR and FGFR).3 TAS-102 is an oral nucleoside antitumor agent that combines trifluridine (FTD), a thymidine-based nucleic acid analogue, and tipiracil hydrochloride (TPI) at a molar ratio of 1:0.5; FTD is the cytotoxic component and TPI is a inhibitor of thymidine phosphorylase.4,5 Cetuximab was the first EGFR-targeting monoclonal antibody (mAb) available in treating mCRC, with panitumumab following several years later. Panitumumab is a fully human mAb of the immunoglobulin (Ig) G2 subtype specific to EGFR.6 All of the drugs above were recommended as single-agent chemotherapy regimens in the National Comprehensive Cancer Network Clinical Practice Guidelines (NCCN Guidelines) for patients exhibiting disease progression after treatment with standard therapies.2
Clinical practice guidance for juvenile idiopathic arthritis (JIA) 2018
Published in Modern Rheumatology, 2019
Nami Okamoto, Shumpei Yokota, Syuji Takei, Yuka Okura, Tomohiro Kubota, Masaki Shimizu, Tomo Nozawa, Naomi Iwata, Hiroaki Umebayashi, Noriko Kinjo, Tomoko Kunishima, Junko Yasumura, Masaaki Mori
Measurement of hepatitis B surface (HBs) antigen (Ag) is performed before starting treatment with immunosuppressive drugs. In HBs-Ag-negative patients, screening for hepatitis B core (HBc) antibody (Ab) and HBs-Ab should be carried out using a high sensitivity assay such as a chemiluminescence immunoassay (CLIA) or chemiluminescence enzyme immunoassay (CLEIA). If either CLIA or CLEIA is positive, a real-time polymerase chain reaction (PCR) should be performed to detect HBV DNA. It is necessary to consult with pediatric rheumatologists and hepatologists immediately if a nucleic acid analogue needs to be administered to HBs-Ag-positive patients or to HBs-Ag-negative patients who are nonetheless HBV DNA-positive,
Related Knowledge Centers
- Deoxyribose
- DNA
- Nucleic Acid
- Nucleobase
- Peptide Nucleic Acid
- Phosphate
- Rna
- Triple Helix
- Structural Analog
- Xeno Nucleic Acid