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Introduction to dermatological treatment
Published in Richard Ashton, Barbara Leppard, Differential Diagnosis in Dermatology, 2021
Richard Ashton, Barbara Leppard
Aciclovir, famciclovir and valaciclovir are the systemic antiviral agents in current use for both herpes simplex and herpes zoster infections. They all inhibit phosphorylation of viral thymidine kinase which prevents viral DNA synthesis and virus replication. They are only effective while there is active viral replication and must therefore be given within 48 hours of the onset of vesicles. They can be used for treating: Herpes simplex if the patient has disseminated disease, frequent recurrences, eczema herpeticum or recurrent erythema multiforme.Herpes zoster. This is much less sensitive to these drugs than herpes simplex so bigger doses need to be given.
Radiation Hormesis in Immunity
Published in T. D. Luckey, Radiation Hormesis, 2020
Autoimmune disease (AID) in mice has been greatly alleviated following 3 Gy whole body irradiation.210,645,907 Whole-body exposure of 1 cGy/d for 20 d increased production of effector T cells; this was especially evident in mice with autoimmune disease.420 This concept is supported by the finding that irradiated mice have increased thymidine kinase, an enzyme required for DNA synthesis.274 Its use in human AIDS, with or without bone marrow transplant, has not been reported.
Gene Therapy for Lung Cancer
Published in Kenneth L. Brigham, Gene Therapy for Diseases of the Lung, 2020
Choon Taek Lee, David P. Carbone
HSV-TK and GCV combination has been the most widely investigated combination, and good responses have been observed in animal studies (reviewed in 82). Thymidine kinase is the enzyme responsible for phosphorylation of thymidine, and is involved in the salvage pathway for DNA synthesis. In contrast to cellular thymidine kinase, HSV-TK has an ability to phosphorylate not only thymidine but also several nucleoside analogs, including the guanosine analog ganciclovir. GCV can be phosphoiylated by HSV-TK to the triphosphorylated form. This triphosphorylated GCV enters the DNA synthesis pathway instead of guanosine triphosphate, and blocks DNA synthesis, inducing cell death. In vitro tumor cell line experiments have shown that GCV sensitivity in HSV-TK gene-transduced tumors is at least 1000 times greater than control, nontransduced tumor cell lines. Furthermore, in animal tumor models, HSVTK transduced tumors showed regression after GCV treatment (83).
Thymidine kinase activity levels in serum can identify HR+ metastatic breast cancer patients with a low risk of early progression (SWOG S0226)
Published in Biomarkers, 2023
Mattias Bergqvist, Adrian Nordmark, Amy Williams, Costanza Paoletti, William Barlow, Erin F. Cobain, Rita S. Mehta, Julie R. Gralow, Gabriel N. Hortobagyi, Kathy S. Albain, Lajos Pusztai, Priyanka Sharma, Andrew K. Godwin, Alastair M. Thompson, Daniel F. Hayes, James M. Rae
Thymidine kinase (TK) is a metabolic enzyme fundamentally involved in DNA synthesis that plays a critical role in cell proliferation (Welin et al.2004). In resting G0 cells, TK activity (TKa) is absent. In actively dividing cells, TKa increases in the G1/S transition, peaks in the S phase and then disappears during mitosis. Uncontrolled and increased proliferation is a hallmark of cancer cells. Elevated TKa in breast cancer tissues is associated with worse prognosis (Robertson et al.1990). In addition to tissue expression, TKa can be measured in circulation and is frequently elevated in patients with cancer compared to normal, healthy individuals. Healthy individuals typically have very low levels of TKa. By contrast, patients with cancer frequently have elevated serum TKa levels indicating increased cell proliferation. Elevated serum TKa levels serve as a marker of increased tumour growth in patients with malignancies and may precede imaging RECIST (Response Evaluation Criteria In Solid Tumors)-determined disease progression by several months (Krishnamurthy et al.2022).
The evolution of cyclin dependent kinase inhibitors in the treatment of cancer
Published in Expert Review of Anticancer Therapy, 2021
Komal Jhaveri, Howard A Burris 3rd, Timothy A Yap, Erika Hamilton, Hope S Rugo, Jonathan W Goldman, Stephen Dann, Feng Liu, Gilbert Y Wong, Heike Krupka, Geoffrey I Shapiro
More recently, a newer generation of oral, potent, and highly selective reversible inhibitors of CDK4 and CDK6 have emerged, including palbociclib, ribociclib, and abemaciclib, established as the standard of care for advanced HR+/HER2– breast cancer combined with hormonal therapy. Pharmacodynamically, CDK4/6 inhibition is demonstrated by reduced RB phosphorylation at Ser780 or Ser807/811 in HR+ breast cancer and mantle cell lymphoma (MCL) [36,37], correlating with reduced proliferation assessed by Ki67 staining. In breast cancer, the serum activity of thymidine kinase 1, the product of an E2F-1-responsive gene secreted into serum by cancer cells, was also shown to be decreased in response to CDK4/6 inhibition [38]. During early treatment, a lack of reduction of these markers can be indicative of intrinsic resistance.
An evaluation of palbociclib as a breast cancer treatment option: a current update
Published in Expert Opinion on Pharmacotherapy, 2021
Gregory T. Gallanis, Ramon I. Pericas, Anna T. Riegel, Paula R. Pohlmann
A benefit of neoadjuvant intervention is that it facilitates the discovery and evaluation of biomarkers that can be correlated with response to treatment, vulnerability to additional therapies, or survival benefit. The phase II NeoPalAna trial evaluated the effects of neoadjuvant palbociclib and anastrozole on tumor cell proliferation and found that palbociclib enhanced cell cycle control, measured by reduced Ki67, regardless of luminal subtype [52]. Subsequent analysis from this trial found that drug-induced suppression of thymidine kinase 1, measured in peripheral serum, correlated with decreased Ki67 levels in these patients [53]. The phase II preoperative-palbociclib (POP) trial examined the effects of 14 days of preoperative palbociclib monotherapy in patients with early breast cancer. Tissue analyses from this trial found that short-term palbociclib treatment decreased protein levels of Ki67 in tumors compared to the no-treatment group, and decreased cyclin E2 mRNA expression correlated with decreased Ki67 levels [54].