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British Journal of Cancer Apr 2022Protein kinase CSNK2 (CK2) is a pleiotropic serine/threonine kinase frequently dysregulated in solid and hematologic malignancies. To consolidate a wide range of... (Review)
Review
Protein kinase CSNK2 (CK2) is a pleiotropic serine/threonine kinase frequently dysregulated in solid and hematologic malignancies. To consolidate a wide range of biological and clinically oriented data from this unique kinase in cancer, this systematic review summarises existing knowledge from in vitro, in vivo and pre-clinical studies on CSNK2 across 24 different human cancer types. CSNK2 mRNA transcripts, protein levels and activity were found to be routinely upregulated in cancer, and commonly identified phosphotargets included AKT, STAT3, RELA, PTEN and TP53. Phenotypically, it frequently influenced evasion of apoptosis, enhancement of proliferation, cell invasion/metastasis and cell cycle control. Clinically, it held prognostic significance across 14 different cancers, and its inhibition in xenograft experiments resulted in a positive treatment response in 12. In conjunction with commentary on preliminary studies of CSNK2 inhibitors in humans, this review harmonises an extensive body of CSNK2 data in cancer and reinforces its emergence as an attractive target for cancer therapy. Continuing to investigate CSNK2 will be crucial to advancing our understanding of CSNK2 biology, and offers the promise of important new discoveries scientifically and clinically.
Topics: Apoptosis; Casein Kinase II; Cell Cycle Checkpoints; Cell Proliferation; Humans; Neoplasms
PubMed: 34773100
DOI: 10.1038/s41416-021-01616-2 -
Annals of Oncology : Official Journal... Apr 2016Borderline ovarian tumors (BOT) are epithelial tumors of the ovaries with both malignant and non-malignant aspects. On the one hand, they are characterized by cellular... (Review)
Review
BACKGROUND
Borderline ovarian tumors (BOT) are epithelial tumors of the ovaries with both malignant and non-malignant aspects. On the one hand, they are characterized by cellular proliferation and nuclear atypia but, on the other hand, they usually do not show infiltrative growth pattern. Balancing radicality between oncologic safety and treatment burden has already led to remarkable changes in the management pattern over the last decades and is still a challenging task.
DESIGN
This review is based on both a systematic review published by the authors and added with evidence gained from actually published literature.
RESULTS
As they frequently affect younger patients, the clinical management of BOT is complicated by aspects as preserving fertility and reducing postoperative morbidity. Over the past decades, the surgical therapy shifted from a radical approach to more conservative treatment. Today, fertility-sparing surgery is first-choice treatment in younger patients. In addition, minimal-invasive surgery has become the preferred surgical approach in these patients. Even recurrences are curable in most patients because only a minority of relapses transform to invasive cancer.
CONCLUSION
More studies on BOT are needed and longer follow-up and better characterization of high-risk subtypes are crucial to better understand long-term risk of BOT and avoid the rare but the fatal outcome in those few patients being undertreated by the current management strategies.
Topics: Disease Management; Female; Fertility Preservation; Humans; Neoplasm Staging; Ovarian Neoplasms; Ovariectomy; Ovary
PubMed: 27141065
DOI: 10.1093/annonc/mdw090 -
Exploration of Targeted Anti-tumor... 2023One in eight fatalities globally are considered cancer-related. The need for cancer therapy is growing. Natural products continue to play a role in drug development, as... (Review)
Review
AIM
One in eight fatalities globally are considered cancer-related. The need for cancer therapy is growing. Natural products continue to play a role in drug development, as up to 50% of authorized drugs in the last 30 years have been isolated from natural sources.
METHODS
Anticancer, antioxidant, antibacterial, antifungal, antiviral, analgesic, anti-inflammatory, and other actions have all been reported in research papers using plants from the genus in the treatment and prevention of disease.
RESULTS
Results from the anticancer test showed that the genus, especially , and had significant promise as an anticancer agent against several cancer cell lines. Numerous factors, including phytochemical composition, increased apoptotic activity, decreased cell proliferation, stopped angiogenesis, and reduced inflammation.
CONCLUSIONS
These results, despite preliminary, show promise for further purification and investigation of bioactive compounds and extracts within the genus for their anticancer properties.
PubMed: 37205310
DOI: 10.37349/etat.2023.00134 -
Frontiers in Genetics 2022Exosomes are nano-extracellular vesicles secreted by a variety of cells. They are composed of a double-layer membrane that can transport a variety of proteins, coding...
Exosomes are nano-extracellular vesicles secreted by a variety of cells. They are composed of a double-layer membrane that can transport a variety of proteins, coding and non-coding genes, and bioactive substances. Exosomes participate in information transmission between cells and regulate processes such as cell proliferation, migration, angiogenesis, and phenotypic transformation. They have broad prospects in the occurrence, development, and treatment of many diseases including orthopedics. Exosomes derived from different types of bone cells such as mesenchymal stem cells, osteoblasts, osteoclasts, and their precursors are recognized to play pivotal roles in bone remodeling processes including osteogenesis, osteoclastogenesis, and angiogenesis. This articlesummarizes the characteristics of exosomes and their research progress in bone remodeling, bone tumors, vascular skeletal muscle injury, spinal cord injury, degenerative disc diseases, cartilage degeneration, osteoarthritis, necrosis of the femoral head, and osteoporosis.
PubMed: 36081990
DOI: 10.3389/fgene.2022.915141 -
Journal of Clinical Epidemiology Apr 2023Systematic reviews and meta-analyses are proliferating as they are an important building block to inform evidence-based guidelines and decision-making. Enforcement of... (Review)
Review
OBJECTIVES
Systematic reviews and meta-analyses are proliferating as they are an important building block to inform evidence-based guidelines and decision-making. Enforcement of best practice in clinical trials is firmly on the research agenda of good clinical practice, but there is less clarity as to how evidence syntheses that combine these studies can be influenced by bad practice. Our aim was to conduct a living systematic review of articles that highlight flaws in published systematic reviews to formally document and understand these problems.
STUDY DESIGN AND SETTING
We conducted a comprehensive assessment of all literature examining problems, which relate to published systematic reviews.
RESULTS
The first iteration of our living systematic review (https://systematicreviewlution.com/) has found 485 articles documenting 67 discrete problems relating to the conduct and reporting of systematic reviews which can potentially jeopardize their reliability or validity.
CONCLUSION
Many hundreds of articles highlight that there are many flaws in the conduct, methods, and reporting of published systematic reviews, despite the existence and frequent application of guidelines. Considering the pivotal role that systematic reviews have in medical decision-making due to having apparently transparent, objective, and replicable processes, a failure to appreciate and regulate problems with these highly cited research designs is a threat to credible science.
Topics: Humans; Reproducibility of Results; Systematic Reviews as Topic
PubMed: 36796736
DOI: 10.1016/j.jclinepi.2023.01.011 -
Indian Journal of Dental Research :... 2017The distinguishing feature of cancer cells is their ability to proliferate indefinitely, which is in contrast to the restricted cell multiplication potential for somatic... (Review)
Review
BACKGROUND
The distinguishing feature of cancer cells is their ability to proliferate indefinitely, which is in contrast to the restricted cell multiplication potential for somatic cells. A better understanding of this contrasting behavior was provided in the early 1990s with the discovery of a relationship between telomeres, telomerase, aging, and cancer. Telomeres (tandem repeat DNA sequence TTAGGG) are protective caps at the ends of human chromosomes. Normal human cells experience telomere shortening with each successive cell division. However, in tumor cells, an overexpression of telomerase confers limitless replicative potential to tumor cells by continuous elongation of telomeres. The objective of this review was to systematically assess the data available on telomerase expression in oral cancer, with special reference to its role in diagnosis, prognosis, and treatment.
MATERIALS AND METHODS
A systematic review of studies that investigated the telomerase expression in oral squamous cell carcinoma (OSCC) was registered with PROSPERO. Subsequent to registration, a predetermined search strategy in accordance with PRISMA guidelines was formulated, and a literature search was conducted using online databases along with hand searching.
RESULTS
Eighty-nine articles from PubMed, 83 from Scopus, 5 from BioMed Central, 43 from Google Scholar, and 2 from hand search were identified. A total of 21 articles were shortlisted that met strict inclusion and exclusion criteria and quality assessment. Each study was evaluated for the markers under study, type of sample used, study design/methodology, and statistical analysis. The studies were then grouped into three subheads depending on their implications in the diagnosis, prognosis, and treatment of OSCC.
CONCLUSION
This review explains the basic biology and the clinical implications of telomerase-based diagnosis and prognosis, the prospects for its use in anticancer therapy, in the context of oral cancer.
Topics: Carcinoma, Squamous Cell; Cell Proliferation; Humans; Mouth Neoplasms; Prognosis; Telomerase; Telomere
PubMed: 29072223
DOI: 10.4103/ijdr.IJDR_690_16 -
Molecules (Basel, Switzerland) Sep 2021We conducted a systematic review of the literature on the effects of cordycepin on cell survival and proliferation, inflammation, signal transduction and animal models.... (Review)
Review
We conducted a systematic review of the literature on the effects of cordycepin on cell survival and proliferation, inflammation, signal transduction and animal models. A total of 1204 publications on cordycepin were found by the cut-off date of 1 February 2021. After application of the exclusion criteria, 791 papers remained. These were read and data on the chosen subjects were extracted. We found 192 papers on the effects of cordycepin on cell survival and proliferation and calculated a median inhibitory concentration (IC) of 135 µM. Cordycepin consistently repressed cell migration (26 papers) and cellular inflammation (53 papers). Evaluation of 76 papers on signal transduction indicated consistently reduced PI3K/mTOR/AKT and ERK signalling and activation of AMPK. In contrast, the effects of cordycepin on the p38 and Jun kinases were variable, as were the effects on cell cycle arrest (53 papers), suggesting these are cell-specific responses. The examination of 150 animal studies indicated that purified cordycepin has many potential therapeutic effects, including the reduction of tumour growth (37 papers), repression of pain and inflammation (9 papers), protecting brain function (11 papers), improvement of respiratory and cardiac conditions (8 and 19 papers) and amelioration of metabolic disorders (8 papers). Nearly all these data are consistent with cordycepin mediating its therapeutic effects through activating AMPK, inhibiting PI3K/mTOR/AKT and repressing the inflammatory response. We conclude that cordycepin has excellent potential as a lead for drug development, especially for age-related diseases. In addition, we discuss the remaining issues around the mechanism of action, toxicity and biodistribution of cordycepin.
Topics: Animals; Antineoplastic Agents; Brain Diseases; Deoxyadenosines; Humans; Inflammation; Metabolic Diseases; Neoplasms; Signal Transduction
PubMed: 34641429
DOI: 10.3390/molecules26195886 -
Frontiers in Endocrinology 2023Reprogramming of cellular metabolism is now a hallmark of tumorigenesis. In recent years, research on pancreatic neuroendocrine tumors (pNETs) has focused on genetic and... (Review)
Review
INTRODUCTION
Reprogramming of cellular metabolism is now a hallmark of tumorigenesis. In recent years, research on pancreatic neuroendocrine tumors (pNETs) has focused on genetic and epigenetic modifications and related signaling pathways, but few studies have been devoted to characterizing the metabolic profile of these tumors. In this review, we thoroughly investigate the metabolic pathways in pNETs by analyzing the transcriptomic and metabolomic data available in the literature.
METHODOLOGY
We retrieved and downloaded gene expression profiles from all publicly available gene set enrichments (GSE43797, GSE73338, and GSE117851) to compare the differences in expressed genes based on both the stage and MEN1 mutational status. In addition, we conducted a systematic review of metabolomic data in NETs.
RESULTS
By combining transcriptomic and metabolomic approaches, we have identified a distinctive metabolism in pNETs compared with controls without pNETs. Our analysis showed dysregulations in the one-carbon, glutathione, and polyamine metabolisms, fatty acid biosynthesis, and branched-chain amino acid catabolism, which supply the tricarboxylic acid cycle. These targets are implicated in pNET cell proliferation and metastasis and could also have a prognostic impact. When analyzing the profiles of patients with or without metastasis, or with or without MEN1 mutation, we observed only a few differences due to the scarcity of published clinical data in the existing research. Consequently, further studies are now necessary to validate our data and investigate these potential targets as biomarkers or therapeutic solutions, with a specific focus on pNETs.
Topics: Humans; Pancreatic Neoplasms; Neuroendocrine Tumors; Prognosis; Epigenesis, Genetic; Neuroectodermal Tumors, Primitive
PubMed: 37908747
DOI: 10.3389/fendo.2023.1248575 -
Cancers Mar 2021Highly proliferative (G3) neuroendocrine neoplasms are divided into well differentiated tumors (NETs) and poorly differentiated carcinomas (NECs), based on the... (Review)
Review
BACKGROUND
Highly proliferative (G3) neuroendocrine neoplasms are divided into well differentiated tumors (NETs) and poorly differentiated carcinomas (NECs), based on the morphological appearance. This systematic review aims to evaluate the clinicopathological features and the treatment response of the NEC subgroup with a Ki67 labeling index (LI) < 55%.
METHODS
A literature search was performed using MEDLINE, Cochrane Library, and Scopus between December 2019 and April 2020, last update in October 2020. We included studies reporting data on the clinicopathological characteristics, survival, and/or therapy efficacy of patients with NECs, in which the Ki67 LI was specified.
RESULTS
8 papers were included, on a total of 268 NEC affected patients. NECs with a Ki67 LI < 55% have been reported in patients of both sexes, mainly of sixth decade, pancreatic origin, and large-cell morphology. The prevalent treatment choice was chemotherapy, followed by surgery and, in only one study, peptide receptor radionuclide therapy. The subgroup of patients with NEC with a Ki67 LI < 55% showed longer overall survival and progression free survival and higher response rates than the subgroup of patients with a tumor with higher Ki67 LI (≥55%).
CONCLUSIONS
NECs are heterogeneous tumors. The subgroup with a Ki67 LI < 55% has a better prognosis and should be treated and monitored differently from NECs with a Ki67 LI ≥ 55%.
PubMed: 33809007
DOI: 10.3390/cancers13061247 -
Cancer Metastasis Reviews Mar 2022The objective of the study was to document the effect of adipocytokines on endometrial cancer progression. A search of the databases CINAHL, Medline, PubMed, Cochrane,... (Review)
Review
The objective of the study was to document the effect of adipocytokines on endometrial cancer progression. A search of the databases CINAHL, Medline, PubMed, Cochrane, Web of Science, Embase and Google Scholar was performed for English language articles from January 2000 to December 2020 using the keywords: (Endometrial cancer) AND (progression OR metastasis) AND (adipocytokine OR adiponectin OR leptin OR visfatin OR IL-6 OR TNF-α OR adipokine OR cytokine). Forty-nine studies on adipocytokines have been included in this review. Adiponectin has been linked with anti-proliferative and anti-metastatic effects on endometrial cancer cells and is associated with a better prognosis. Leptin, visfatin and resistin are linked to the stimulation of endometrial cancer growth, proliferation, invasion and metastasis and are associated with worse prognosis or with a higher grade/stage of endometrial cancer. IL-6, Il-11, IL-31, IL-33, TNF-α, TGF-β1, SDF-1 and CXCR are involved in endometrial cancer cell growth and metastasis or involved in epithelial mesenchymal transformation (EMT) or associated with advanced disease. Adipocytokines have been found to directly impact endometrial cancer cell proliferation, invasion and migration. These molecules and their signalling pathways may be used to determine prognosis and course of the disease and may also be exploited as potential targets for cancer treatment and prevention of progression.
Topics: Adipokines; Adiponectin; Disease Progression; Endometrial Neoplasms; Female; Humans; Interleukin-6; Leptin; Nicotinamide Phosphoribosyltransferase; Tumor Necrosis Factor-alpha
PubMed: 34951691
DOI: 10.1007/s10555-021-10002-6