57,143 results match your criteria cyclin dependent

Functionally active cyclin-dependent kinase 9 is essential for porcine reproductive and respiratory syndrome virus subgenomic RNA synthesis.

Mol Immunol 2021 May 11;135:351-364. Epub 2021 May 11.

College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, China; International Joint Research Center of National Animal Immunology, Henan Agricultural University, Zhengzhou, Henan Province, China. Electronic address:

Cyclin-dependent kinase 9 (CDK9) is a key regulator of RNA-polymerase II and a candidate therapeutic target for various virus infections such as respiratory syncytial virus, herpes simplex virus, human adenovirus, human cytomegalovirus, hepatitis virus B, and human papillomavirus. We employed CDK9-IN-1, a selective CDK9 inhibitor, to investigate the role of CDK9 in porcine reproductive and respiratory syndrome virus (PRRSV) infection. CDK9-IN-1 dose-dependently reduced PRRSV replication without cytotoxicity in the infected cells. Read More

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CDKL5 deficiency disorder in males: Five new variants and review of the literature.

Eur J Paediatr Neurol 2021 Apr 30;33:9-20. Epub 2021 Apr 30.

Paediatric Neurology Unit V. Buzzi Children's Hospital Milan, Italy.

The X-linked Cyclin-Dependent Kinase-Like 5 (CDKL5) gene encodes a serine-threonine kinase highly expressed in the developing brain. Loss of function of CDKL5 is pointed out to underlie the CDKL5 Deficiency Disorder (CDD), an X-linked dominant disease characterized by early-onset epileptic encephalopathy and developmental delay, usually affecting females more than males. To the best to our knowledge, only 45 males with CDD have been reported so far. Read More

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and : GC-based metabolomics for the assessment of seasonal and organ variation in their volatile components, and cytotoxic activity estimation.

Food Funct 2021 May 14. Epub 2021 May 14.

Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, 11562, Cairo, Egypt.

Volatile constituents isolated from the stems (S) and leaves (L) of Pimenta dioica (PD) and Pimenta racemosa (PR) during the four seasons were analyzed using GLC/FID (Gas liquid chromatography - flame ionization detector) and GLC/MS (Gas liquid chromatography - mass spectrometry). Eighty-nine compounds were identified in all samples, in which oxygenated monoterpene represented by eugenol was the major constituent in PDS-S3 (autumn) (88.71%) and PDS-S2 (summer) (88. Read More

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ESM1 promotes triple-negative breast cancer cell proliferation through activating AKT/NF-κB/Cyclin D1 pathway.

Ann Transl Med 2021 Apr;9(7):533

College of Biomedicine and Health, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.

Background: Triple-negative breast cancer (TNBC) is a subtype of invasive breast cancer that tests negative for PR, ER and excess HER2 protein. TNBC has a greater progression potential with poorer prognosis, compared with other types of breast cancer. Endothelial cell-specific molecule 1 (ESM1), also known as endocan, is overexpressed in various cancers including breast cancer and may play an important role in cancer progression. Read More

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Recent Understanding and Future Directions of Recurrent Corticotroph Tumors.

Front Endocrinol (Lausanne) 2021 26;12:657382. Epub 2021 Apr 26.

Neuroendocrinology Clinic, Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

Corticotroph tumors (CTs) are pituitary neoplasms arising from the Tpit lineage, which may or not express adrenocorticotrophic hormone (ACTH). Functioning CTs cause Cushing's disease (CD), which has high morbidity and mortality due to hypercortisolemia. "Non-functioning" or silent CTs (SCT) and the Crooke's cell subtypes do not cause CD and may be asymptomatic until manifested by compressive symptoms and are more frequently found as macroadenoma. Read More

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A Case of Phyllodes Tumor of the Breast with Mixed Liposarcoma: Case Report and Literature Review.

Onco Targets Ther 2021 6;14:3003-3011. Epub 2021 May 6.

Department of Pathology, Shihezi University School of Medicine and the First Affiliated Hospital to Shihezi University School of Medicine, Shihezi, Xinjiang, 832002, People's Republic of China.

Phyllodes tumors (PTs) account for less than 1% of breast tumors, and malignant PTs account for even less. Here, we described an unusual case of malignant PT with mixed liposarcoma (myxoid liposarcoma [MLP] and pleomorphic liposarcoma [PLP]). A 52-year-old woman discovered a small lump in her left breast. Read More

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p27 controls autophagic vesicle trafficking in glucose-deprived cells via the regulation of ATAT1-mediated microtubule acetylation.

Cell Death Dis 2021 May 13;12(5):481. Epub 2021 May 13.

MCD, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, 31062, Toulouse, Cedex, France.

The cyclin-dependent kinase inhibitor p27 (p27) has been involved in promoting autophagy and survival in conditions of metabolic stress. While the signaling cascade upstream of p27 leading to its cytoplasmic localization and autophagy induction has been extensively studied, how p27 stimulates the autophagic process remains unclear. Here, we investigated the mechanism by which p27 promotes autophagy upon glucose deprivation. Read More

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Hormone Resistance.

Jonghan Yu

Adv Exp Med Biol 2021 ;1187:391-401

Breast Division, Department of Surgery, Samsung Medical Center, Seoul, South Korea.

Hormone therapy is a major therapy for hormone receptor-positive breast cancer that improves survival. However, despite these hormone treatments, there are de novo or acquired resistance of breast cancer. Many studies revealed these resistance mechanisms, which are related to hormonal receptors including low expression or mutation of estrogen receptor alpha(ERα), co-factors and progesterone receptor, and with activation of growth signaling pathways such as PIK3A/Akt/mTOR pathway or cell cycle pathway. Read More

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January 2021

Lupus susceptibility region containing CDKN1B rs34330 mechanistically influences expression and function of multiple target genes, also linked to proliferation and apoptosis.

Arthritis Rheumatol 2021 May 13. Epub 2021 May 13.

Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.

Objective: A recent genome-wide association study (GWAS) reported a significant genetic association between rs34330 of cyclin-dependent kinase inhibitor 1B (CDKN1B) and risk of systemic lupus erythematosus (SLE) in Han Chinese. This study aims to validate the reported association and elucidate the biochemical mechanisms underlying the variant's effect.

Methods: We performed allelic association with SLE followed by meta-analysis across 11 independent cohorts (n=28,872). Read More

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A curcumin analogue GL63 inhibits the malignant behaviors of hepatocellular carcinoma by inactivating the JAK2/STAT3 signaling pathway via the circZNF83/miR-324-5p/CDK16 axis.

J Gastroenterol Hepatol 2021 May 12. Epub 2021 May 12.

Department of Burn and Plastic Surgery, The First Hospital, Hebei Medical University, Shijiazhuang, China.

Background: (1E,4E)-1,5-bis(2-bromophenyl) penta-1,4-dien-3-one (GL63) is a curcumin analogue that can protect against carcinogenesis in hepatocellular carcinoma (HCC). The aim of this study was to explore the molecular mechanism of GL63 in HCC.

Methods: Cell viability was examined by Cell Counting Kit-8 (CCK-8) assay. Read More

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Gene Expression as a Potential Aging Biomarker in Dogs.

Front Vet Sci 2021 26;8:660435. Epub 2021 Apr 26.

Department of Ethology, Senior Family Dog Project, ELTE Eötvös Loránd University, Budapest, Hungary.

Describing evolutionary conserved physiological or molecular patterns, which can reliably mark the age of both model organisms and humans or predict the onset of age-related pathologies has become a priority in aging research. The age-related gene-expression changes of the () gene have been well-documented in humans and rodents. However, data is lacking from other relevant species, including dogs. Read More

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Novel Murine Biomarkers of Radiation Exposure Using An Aptamer-Based Proteomic Technology.

Front Pharmacol 2021 26;12:633131. Epub 2021 Apr 26.

Radiation Oncology Branch, National Cancer Institute, Bethesda, MD, United States.

There is a need to identify new biomarkers of radiation exposure both for use in the development of biodosimetry blood diagnostics for radiation exposure and for clinical use as markers of radiation injury. In the current study, a novel high-throughput proteomics screening approach was used to identify proteomic markers of radiation exposure in the plasma of total body irradiated mice. A subset panel of significantly altered proteins was selected to build predictive models of radiation exposure and received radiation dose useful for population screening in a future radiological or nuclear event. Read More

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C646 inhibits G2/M cell cycle-related proteins and potentiates anti-tumor effects in pancreatic cancer.

Sci Rep 2021 May 12;11(1):10078. Epub 2021 May 12.

Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.

The activity of histone acetyltransferases (HATs) plays a central role in an epigenetic modification in cooperation with HDACs (histone deacetyl transferases). It is likely that malfunction of this enzymatic machinery controlling epigenetic modification is relevant to carcinogenesis and tumor progression. However, in pancreatic cancer, the clinical relevance of HAT activity and histone acetylation has remained unclear. Read More

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LncRNA-CCDC144NL-AS1 Promotes the Development of Hepatocellular Carcinoma by Inducing WDR5 Expression via Sponging miR-940.

J Hepatocell Carcinoma 2021 3;8:333-348. Epub 2021 May 3.

Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People's Republic of China.

Purpose: This work was initiated to offer solid evidence regarding the expression and roles of long noncoding RNA (lncRNA) CCDC144NL-AS1 in hepatocellular carcinoma (HCC).

Patients And Methods: Cell Counting Kit-8 assay, flow cytometric analysis, and invasion assays were used to explore the malignant biological characteristics of cells. Immunohistochemistry (IHC), Western blotting analysis, and real-time quantitative PCR (RT-qPCR) were used to analyze the expression level of related proteins and nucleic acids. Read More

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Advances in Therapy for Hormone Receptor (HR)-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Advanced Breast Cancer Patients Who Have Experienced Progression After Treatment with CDK4/6 Inhibitors.

Chao Li Xujun Li

Onco Targets Ther 2021 3;14:2929-2939. Epub 2021 May 3.

Department of Breast Surgery, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, 315000, People's Republic of China.

Approximately 70% of breast cancer (BC) cases are hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) BC. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have acted as star drugs for reversing endocrine therapy (ET) resistance and improving the prognosis of patients with HR+ advanced breast cancer (ABC) since they were initially approved. However, progression eventually occurs. Read More

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Senescence-associated secretory phenotype and activation of NF-κB in splenocytes of old mice exposed to irradiation at a young age.

Dev Comp Immunol 2021 May 8:104124. Epub 2021 May 8.

Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan. Electronic address:

DNA damage-induced cellular senescence is involved in aging. We reported previously that p53 mice subjected to irradiation at a young age exhibited an increased number of splenic lymphocytes in the S and G2/M phases. However, the detailed nature of splenic disorders in these mice is not fully understood. Read More

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Control of multiciliogenesis by miR-34/449 in the male reproductive tract through enforcing cell cycle exit.

J Cell Sci 2021 May 11;134(9). Epub 2021 May 11.

Department of Histoembryology, Genetics and Developmental Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Multiciliated cells (MCCs) are terminally differentiated postmitotic cells that possess hundreds of motile cilia on their apical surface. Defects in cilia formation are associated with ciliopathies that affect many organs. In this study, we tested the role and mechanism of the miR-34/449 family in the regulation of multiciliogenesis in EDs using an miR-34b/c-/-; miR-449-/- double knockout (dKO) mouse model. Read More

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Restraining CDK1-cyclin B activation: PP2A on the cUSP(7).

EMBO J 2021 May 10:e108486. Epub 2021 May 10.

Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.

USP7 inhibitors are gaining momentum as a therapeutic strategy to stabilize p53 through their ability to induce MDM2 degradation. However, these inhibitors come with an unexpected p53-independent toxicity, via an unknown mechanism. In this issue of The EMBO Journal, Galarreta et al report how inhibition of USP7 leads to re-distribution of PP2A from cytoplasm to nucleus and an increase of deleterious CDK1-dependent phosphorylation throughout the cell cycle, revealing a new regulatory mechanism for the progression of S-phase cells toward mitosis to maintain genomic integrity. Read More

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ESMO 2020: highlights in breast cancer.

Rupert Bartsch

Memo 2021 Apr 30:1-4. Epub 2021 Apr 30.

Department of Medicine 1, Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.

Despite the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, results of several pertinent studies in the field of breast cancer (BC) were presented in a virtual format at the 2020 European Society of Medical Oncology (ESMO) Congress. Early results of the MonarchE trial investigating the addition of the cyclin-dependent kinase (CDK) 4/6 inhibitor abemaciclib to standard adjuvant endocrine therapy indicated a lower recurrence rate in the combination group in a high-risk population of patients with early stage hormone receptor (HR)-positive/HER2-negative BC. In contrast, the PALLAS study evaluating adjuvant palbociclib could not confirm these results. Read More

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Incaspitolide A isolated from L. inhibits the growth of prostate cancer cells and induces apoptosis via regulation of the PI3K/Akt/xIAP pathway.

Oncol Lett 2021 Jun 19;21(6):477. Epub 2021 Apr 19.

College of Pharmaceutical Sciences, Southwest University, Chongqing, Sichuan 400715, P.R. China.

L. is a traditional medicine primarily used in Southwestern China, and it has been shown to exhibit a range of biological properties, including anti-inflammatory and antitumor activities. Incaspitolide A (IA) is a sesquiterpene isolated from L. Read More

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Targeting cell cycle regulation via the G2-M checkpoint for synthetic lethality in melanoma.

Cell Cycle 2021 May 9:1-11. Epub 2021 May 9.

Department of Human Science, Georgetown University, Washington, DC, USA.

Disruption of cell cycle checkpoints has been well established as a hallmark of cancer. In particular, the G1-S transition mediated by the cyclin D-cyclin-dependent kinase 4/6 (CDK4/6) pathway is dysregulated in more than 90% of melanoma cases. Therefore, tumor cells mainly rely on the G2-M checkpoint to halt the cell cycle in order to repair DNA damage. Read More

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The risk variant of CDKAL1 (rs7756992) impairs fasting glucose levels and insulin resistance improvements after a partial meal-replacement hypocaloric diet.

Endocrinol Diabetes Nutr 2021 May 5. Epub 2021 May 5.

Servicio de Endocrinología y Nutrición, Hospital Clínico Universitario de Valladolid. Centro de Investigación de Endocrinología y Nutrición Clínica, Facultad de Medicina, Universidad de Valladolid, Valladolid, España. Electronic address:

Background: The CDKAL1 (CDK5 Regulatory Subunit Associated Protein 1 Like 1) gene encodes cyclin-dependent kinase 5 (CDK5) regulatory subunit-associated proten1 like 1. This protein has been shown to contribute to the glucose-dependent regulation of insulin secretion in pancreatic islets.

Aims: The aim of our study was to analyze the effects of the rs7756992 genetic variant of CDKAL1 gene on fasting glucose and insulin resistance after weight loss secondary to partial meal replacement hypocaloric diet (pMRHD). Read More

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Identification of pseudolaric acid B as a novel Hedgehog pathway inhibitor in medulloblastoma.

Biochem Pharmacol 2021 May 5:114593. Epub 2021 May 5.

Institute of Clinical Pharmacology, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Research Center of Chinese Herbal Resources Science and Engineering, School of Pharmaceutical Sciences, Key Laboratory of Chinese Medicinal Resource from Lingnan, Ministry of Education, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. Electronic address:

Aberrant activation of the Hedgehog (Hh) pathway is implicated in the pathogenesis and development of multiple cancers, especially Hh-driven medulloblastoma (MB). Smoothened (SMO) is a promising therapeutic target of the Hh pathway in clinical cancer treatment. However, SMO mutations frequently occur, which leads to drug resistance and tumor relapse. Read More

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The early evolutionary landscape of osteosarcoma provides clues for targeted treatment strategies.

J Pathol 2021 May 8. Epub 2021 May 8.

Bone Tumor Reference Centre, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Schönbeinstrasse 40, 4056, Basel, Switzerland.

Osteosarcomas are aggressive primary tumors of bone that are typically detected in locally advanced stages, however which genetic mutations drive the cancer before its clinical detection remain unknown. To identify these events, we perform longitudinal genome-sequencing analysis of 12 patients with metastatic or refractory osteosarcoma. Phylogenetic and molecular clock analyses are carried out next to identify actionable mutations, and these are validated by integrating data from additional 153 osteosarcomas and pre-existing functional evidence from mouse PDX models. Read More

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The transcriptome of wild-type and immortalized corneal epithelial cells.

Sci Data 2021 May 7;8(1):126. Epub 2021 May 7.

Graduate School of Science and Engineering, Iwate University, 4-3-5 Ueda, Morioka, Iwate, 020-8551, Japan.

Cellular immortalization enables indefinite expansion of cultured cells. However, the process of cell immortalization sometimes changes the original nature of primary cells. In this study, we performed expression profiling of poly A-tailed RNA from primary and immortalized corneal epithelial cells expressing Simian virus 40 large T antigen (SV40) or the combination of mutant cyclin-dependent kinase 4 (CDK4), cyclin D1, and telomere reverse transcriptase (TERT). Read More

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Phosphorylation of islet-1 serine 269 by CDK1 increases its transcriptional activity and promotes cell proliferation in gastric cancer.

Mol Med 2021 May 7;27(1):47. Epub 2021 May 7.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education of China, Peking University, Beijing, P. R. China.

Background: Despite recent advances in diagnostic and therapeutic approaches for gastric cancer (GC), the survival of patients with advanced GC remains very low. Islet-1 (ISL1) is a LIM-homeodomain transcription factor, which is upregulated and promotes cell proliferation in GC. The exact mechanism by which ISL1 influences GC development is unclear. Read More

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The barley SHN1-type transcription factor HvSHN1 imparts heat, drought and salt tolerances in transgenic tobacco.

Plant Physiol Biochem 2021 May 1;164:44-53. Epub 2021 May 1.

Laboratory of Plant Biotechnology and Improvement, University of Sfax, Center of Biotechnology of Sfax, Route Sidi Mansour, Km 6 B.P' 1177, 3018 Sfax, Tunisia. Electronic address:

The APETAL2/Ethylene Responsive Factor (AP2/ERF) family was the subject of intensive research which led to the identification of several members involved in different stress responses such as salinity, drought and high temperature. The SHN/WIN clade of AP2/ERF participates in many important processes such as cutin and wax biosynthesis, ethylene signaling and gene expression. Here, we report the functional analysis of SHN1-type transcription factor, HvSHN1, from barely. Read More

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Dasatinib inhibits proliferation of liver cancer cells, but activation of Akt/mTOR compromises dasatinib as a cancer drug.

Acta Biochim Biophys Sin (Shanghai) 2021 May 7. Epub 2021 May 7.

Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China.

Dasatinib is a multi-target protein tyrosine kinase inhibitor. Due to its potent inhibition of Src, Abl, the platelet-derived growth factor receptor (PDGFR) family kinases, and other oncogenic kinases, it has been investigated as a targeted therapy for a broad spectrum of cancer types. However, its efficacy has not been significantly extended beyond leukemia. Read More

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CDK5 positively regulates Notch1 signaling in pancreatic cancer cells by phosphorylation.

Cancer Med 2021 May 7. Epub 2021 May 7.

Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China.

The marked overexpression of cyclin-dependent kinase 5 (CDK5) or Notch1 receptor, which plays critical roles in pancreatic ductal adenocarcinoma (PDAC) development, has been detected in numerous PDAC cell lines and tissues. Although, a previous study has demonstrated that CDK5 inhibition disrupts Notch1 functions in human umbilical vein endothelial cells, the mechanism underlying Notch1 activation regulated by CDK5 remains unclear. Herein, we identified a physical interaction between CDK5 and Notch1 in PDAC cells, with the Notch1 peptide phosphorylated by CDK5/p25 kinase. Read More

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