Cyclin-Dependent Kinase Inhibitors and Combination Therapy: Experimental and Clinical Status

2006 ◽  
pp. 389-406
Keyword(s):  
Combination Therapy ◽  
Kinase Inhibitors ◽  
Clinical Status ◽  
Cyclin Dependent Kinase

scholarly journals The Individual Effects of Cyclin-Dependent Kinase Inhibitors on Head and Neck Cancer Cells—A Systematic Analysis

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2396
Author(s):  
Nina Schoenwaelder ◽  
Inken Salewski ◽  
Nadja Engel ◽  
Mareike Krause ◽  
Björn Schneider ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Head And Neck ◽  
Kinase Inhibitors ◽  
In Vivo Studies ◽  
Specific Response ◽  
Cyclin Dependent Kinase ◽  
Systematic Analysis ◽  
Mhc I ◽  
Oncological Treatment

Cyclin-dependent kinase inhibitors (CDKi´s) display cytotoxic activity against different malignancies, including head and neck squamous cell carcinomas (HNSCC). By coordinating the DNA damage response, these substances may be combined with cytostatics to enhance cytotoxicity. Here, we investigated the influence of different CDKi´s (palbociclib, dinaciclib, THZ1) on two HNSCC cell lines in monotherapy and combination therapy with clinically-approved drugs (5-FU, Cisplatin, cetuximab). Apoptosis/necrosis, cell cycle, invasiveness, senescence, radiation-induced γ-H2AX DNA double-strand breaks, and effects on the actin filament were studied. Furthermore, the potential to increase tumor immunogenicity was assessed by analyzing Calreticulin translocation and immune relevant surface markers. Finally, an in vivo mouse model was used to analyze the effect of dinaciclib and Cisplatin combination therapy. Dinaciclib, palbociclib, and THZ1 displayed anti-neoplastic activity after low-dose treatment, while the two latter substances slightly enhanced radiosensitivity. Dinaciclib decelerated wound healing, decreased invasiveness, and induced MHC-I, accompanied by high amounts of surface-bound Calreticulin. Numbers of early and late apoptotic cells increased initially (24 h), while necrosis dominated afterward. Antitumoral effects of the selective CDKi palbociclib were weaker, but combinations with 5-FU potentiated effects of the monotherapy. Additionally, CDKi and CDKi/chemotherapy combinations induced MHC I, indicative of enhanced immunogenicity. The in vivo studies revealed a cell line-specific response with best tumor growth control in the combination approach. Global acting CDKi’s should be further investigated as targeting agents for HNSCC, either individually or in combination with selected drugs. The ability of dinaciclib to increase the immunogenicity of tumor cells renders this substance a particularly interesting candidate for immune-based oncological treatment regimens.

scholarly journals Effect of Aprotinin and Avifavir® Combination Therapy for Moderate COVID-19 Patients

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1253
Author(s):  
Andrey A. Ivashchenko ◽  
Valeria N. Azarova ◽  
Alina N. Egorova ◽  
Ruben N. Karapetian ◽  
Dmitry V. Kravchenko ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Body Temperature ◽  
Combination Therapy ◽  
Serine Proteases ◽  
Clinical Status ◽  
Single Center ◽  
Single Center Study ◽  
D Dimer ◽  
Center Study

COVID-19 is a contagious multisystem inflammatory disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We studied the efficacy of Aprotinin (nonspecific serine proteases inhibitor) in combination with Avifavir® or Hydroxychloroquine (HCQ) drugs, which are recommended by the Russian Ministry of Health for the treatment therapy of moderate COVID-19 patients. This prospective single-center study included participants with moderate COVID-19-related pneumonia, laboratory-confirmed SARS-CoV-2, and admitted to the hospitals. Patients received combinations of intravenous (IV) Aprotinin (1,000,000 KIU daily, 3 days) and HCQ (cohort 1), inhalation (inh) treatment with Aprotinin (625 KIU four times per day, 5 days) and HCQ (cohort 2) or IV Aprotinin (1,000,000 KIU daily for 5 days) and Avifavir (cohort 3). In cohorts 1–3, the combination therapy showed 100% efficacy in preventing the transfer of patients (n = 30) to the intensive care unit (ICU). The effect of the combination therapy in cohort 3 was the most prominent, and the median time to SARS-CoV-2 elimination was 3.5 days (IQR 3.0–4.0), normalization of the CRP concentration was 3.5 days (IQR 3–5), of the D-dimer concentration was 5 days (IQR 4 to 5); body temperature was 1 day (IQR 1–3), improvement in clinical status or discharge from the hospital was 5 days (IQR 5–5), and improvement in lung lesions of patients on 14 day was 100%.

Expression and mutational analysis of Cip/Kip family in early glottic cancer

2015 ◽  
Vol 129 (2) ◽  
pp. 168-173 ◽  
Author(s):  
D-K Kim ◽  
J H Lee ◽  
O J Lee ◽  
C H Park
Keyword(s):  
Dna Methylation ◽  
Polymerase Chain Reaction ◽  
Kinase Inhibitors ◽  
Mutational Analysis ◽  
Glottic Cancer ◽  
Cyclin Dependent Kinase ◽  
Chain Reaction ◽  
Single Strand Conformational Polymorphism ◽  
Early Glottic Cancer ◽  
Polymerase Chain

AbstractBackground:Genetic alteration of cyclin-dependent kinase inhibitors has been associated with carcinogenesis mechanisms in various organs.Objective:This study aimed to evaluate the expression and mutational analysis of Cip/Kip family cyclin-dependent kinase inhibitors (p21CIP1/WAF1, p27KIP1 and p57KIP2) in early glottic cancer.Methods:Expressions of Cip/Kip family and p53 were determined by quantitative reverse transcription polymerase chain reaction and densitometry. For the analysis of p21 inactivation, sequence alteration was assessed using single-strand conformational polymorphism polymerase chain reaction. Additionally, the inactivation mechanism of p27 and p57 were investigated using DNA methylation analysis.Results:Reduced expression of p27 and p57 were detected in all samples, whereas the expression of p21 was incompletely down-regulated in 6 of 11 samples. Additionally, single-strand conformational polymorphism polymerase chain reaction analysis showed the p53 mutation at exon 6. Methylation of p27 and p57 was detected by DNA methylation assay.Conclusion:Our results suggest that the Cip/Kip family may have a role as a molecular mechanism of carcinogenesis in early glottic cancer.

scholarly journals Quo Vadis Advanced Prostate Cancer Therapy? Novel Treatment Perspectives and Possible Future Directions

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2228
Author(s):  
Jana Kvízová ◽  
Vladimíra Pavlíčková ◽  
Eva Kmoníčková ◽  
Tomáš Ruml ◽  
Silvie Rimpelová
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Kinase Inhibitors ◽  
Diagnostic Methods ◽  
Common Disease ◽  
Cyclin Dependent Kinase ◽  
Future Directions ◽  
Prostate Cancer Therapy ◽  
Quo Vadis ◽  
Antiandrogen Therapy

Prostate cancer is a very common disease, which is, unfortunately, often the cause of many male deaths. This is underlined by the fact that the early stages of prostate cancer are often asymptomatic. Therefore, the disease is usually detected and diagnosed at late advanced or even metastasized stages, which are already difficult to treat. Hence, it is important to pursue research and development not only in terms of novel diagnostic methods but also of therapeutic ones, as well as to increase the effectiveness of the treatment by combinational medicinal approach. Therefore, in this review article, we focus on recent approaches and novel potential tools for the treatment of advanced prostate cancer; these include not only androgen deprivation therapy, antiandrogen therapy, photodynamic therapy, photothermal therapy, immunotherapy, multimodal therapy, but also poly(ADP-ribose) polymerase, Akt and cyclin-dependent kinase inhibitors.

A current and comprehensive review of cyclin-dependent kinase inhibitors for the treatment of metastatic breast cancer

2017 ◽  
Vol 33 (9) ◽  
pp. 1559-1569 ◽  
Author(s):  
Burak Bilgin ◽  
Mehmet A.N. Sendur ◽  
Didem Şener Dede ◽  
Muhammed Bülent Akıncı ◽  
Bülent Yalçın
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Kinase Inhibitors ◽  
Metastatic Breast ◽  
Cyclin Dependent Kinase ◽  
Comprehensive Review ◽  
A Current
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