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Farmacia Hospitalaria : Organo Oficial... 2023Several studies quantitatively described patients with Chronic Myeloid Leukemia on active treatment with tyrosine kinase inhibitors, however there are few qualitative... (Review)
Review
OBJECTIVE
Several studies quantitatively described patients with Chronic Myeloid Leukemia on active treatment with tyrosine kinase inhibitors, however there are few qualitative studies that focus their results on how to accompany patients in the course of the disease over time. The objective of this review is to find out what are the expectations, information needs and experiences that determine adherence to treatment with tyrosine kinase inhibitors in patients with Chronic Myeloid Leukemia in qualitative research articles published in the scientific literature.
METHODS
A systematic review of qualitative research articles published between 2003-2021 was carried out in PubMed/Medline, Web of Science and Embase databases. Main keywords used were: "Leukemia, Myeloid" and "Qualitative Research". Articles on the acute phase or blast phase were excluded.
RESULTS
184 publications were located. After elimination of duplicates, 6 (3%) were included and 176 (97%) publications were excluded. Studies show that the illness is a turning point in patients' lives, and they develop their own strategies for managing the adverse effects. The factors that determine medication experiences with tyrosine kinase inhibitors should be addressed by implementing personalized strategies: this would result in early detection of problems, reinforce education at each stage and promote open discussion about complex causes underlying the treatment failure.
CONCLUSIONS
This systematic review provides evidence that implementation personalized strategies must be done to adress the factors that determine the illness experience with Chronic Myeloid Leukemia and receiving treatment with tyrosine kinase inhibitors.
Topics: Humans; Antineoplastic Agents; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Drug-Related Side Effects and Adverse Reactions; Fusion Proteins, bcr-abl
PubMed: 36870818
DOI: 10.1016/j.farma.2023.02.002 -
Cells Jun 2023Tumor endothelial cells (TECs) are key stromal components of the tumor microenvironment, and are essential for tumor angiogenesis, growth and metastasis. Accumulating... (Review)
Review
Tumor endothelial cells (TECs) are key stromal components of the tumor microenvironment, and are essential for tumor angiogenesis, growth and metastasis. Accumulating evidence has shown that small single-stranded non-coding microRNAs (miRNAs) act as powerful endogenous regulators of TEC function and blood vessel formation. This systematic review provides an up-to-date overview of these endothelial miRNAs. Their expression is mainly regulated by hypoxia, pro-angiogenic factors, gap junctions and extracellular vesicles, as well as long non-coding RNAs and circular RNAs. In preclinical studies, they have been shown to modulate diverse fundamental angiogenesis-related signaling pathways and proteins, including the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway; the rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway; the phosphoinositide 3-kinase (PI3K)/AKT pathway; and the transforming growth factor (TGF)-β/TGF-β receptor (TGFBR) pathway, as well as krüppel-like factors (KLFs), suppressor of cytokine signaling (SOCS) and metalloproteinases (MMPs). Accordingly, endothelial miRNAs represent promising targets for future anti-angiogenic cancer therapy. To achieve this, it will be necessary to further unravel the regulatory and functional networks of endothelial miRNAs and to develop safe and efficient TEC-specific miRNA delivery technologies.
Topics: Humans; MicroRNAs; Endothelial Cells; Vascular Endothelial Growth Factor A; Phosphatidylinositol 3-Kinases; Neoplasms; Mitogen-Activated Protein Kinase Kinases; Receptors, Vascular Endothelial Growth Factor; Tumor Microenvironment
PubMed: 37443725
DOI: 10.3390/cells12131692 -
Biochemical Society Transactions Jun 2021Hypoxia is a feature of most solid tumours and predicts for poor prognosis. In radiobiological hypoxia (<0.1% O2) cells become up to three times more resistant to...
Hypoxia is a feature of most solid tumours and predicts for poor prognosis. In radiobiological hypoxia (<0.1% O2) cells become up to three times more resistant to radiation. The biological response to radiobiological hypoxia is one of few physiologically relevant stresses that activates both the unfolded protein and DNA damage responses (UPR and DDR). Links between these pathways have been identified in studies carried out in normoxia. Based in part on these previous studies and recent work from our laboratory, we hypothesised that the biological response to hypoxia likely includes overlap between the DDR and UPR. While inhibition of the DDR is a recognised strategy for improving radiation response, the possibility of achieving this through targeting the UPR has not been realised. We carried out a systematic review to identify links between the DDR and UPR, in human cell lines exposed to <2% O2. Following PRISMA guidance, literature from January 2010 to October 2020 were retrieved via Ovid MEDLINE and evaluated. A total of 202 studies were included. LAMP3, ULK1, TRIB3, CHOP, NOXA, NORAD, SIAH1/2, DYRK2, HIPK2, CREB, NUPR1, JMJD2B, NRF2, GSK-3B, GADD45a, GADD45b, STAU1, C-SRC, HK2, CAV1, CypB, CLU, IGFBP-3 and SP1 were highlighted as potential links between the hypoxic DDR and UPR. Overall, we identified very few studies which demonstrate a molecular link between the DDR and UPR in hypoxia, however, it is clear that many of the molecules highlighted warrant further investigation under radiobiological hypoxia as these may include novel therapeutic targets to improve radiotherapy response.
Topics: Animals; Apoptosis; Cell Line, Tumor; DNA Damage; Humans; Hypoxia; Neoplasms; Protein Serine-Threonine Kinases; Signal Transduction; Unfolded Protein Response
PubMed: 34003246
DOI: 10.1042/BST20200861 -
Haematologica Jan 2013Second generation tyrosine kinase inhibitors have recently been introduced as first-line treatment for chronic phase chronic myelogenous leukemia. We aimed to evaluate... (Meta-Analysis)
Meta-Analysis Review
Has the time for first-line treatment with second generation tyrosine kinase inhibitors in patients with chronic myelogenous leukemia already come? Systematic review and meta-analysis.
Second generation tyrosine kinase inhibitors have recently been introduced as first-line treatment for chronic phase chronic myelogenous leukemia. We aimed to evaluate the efficacy and safety of 2(nd) generation tyrosine kinase inhibitors versus imatinib as first-line treatment for these patients. We carried out a systematic review and meta-analysis of randomized controlled trials comparing 2(nd) generation tyrosine kinase inhibitors to imatinib as first-line treatment in chronic phase chronic myelogenous leukemia patients. Outcomes assessed were: complete cytogenetic response and major molecular response at 12, 18 and 24 months, all-cause mortality and progression to accelerated phase/blastic crisis at 12, 18 and 24 months, and chronic myelogenous leukemia related mortality and toxicity at last follow up. Relative risks were estimated and pooled using a fixed effect model. Our search yielded four trials including 2,120 patients. At 12 months, treatment with 2(nd) generation tyrosine kinase inhibitors significantly improved both complete cytogenetic response and major molecular response (relative risk 1.16, 95% CI: 1.09-1.23, and 1.68, 95% CI: 1.48-1.91, respectively). While major molecular response was improved at all time points, complete cytogenetic response improved at 18 months but not at 24 months. Importantly, rate of progression to accelerated phase/blastic crisis was significantly lower with the newer tyrosine kinase inhibitors throughout all time points. Second generation tyrosine kinase inhibitors improved chronic myelogenous leukemia related mortality without a statistically significant difference in all-cause mortality at 12, 18 and 24 months. We conclude that 2(nd) generation tyrosine kinase inhibitors can be added safely to the first-line treatment armamentarium of chronic phase chronic myelogenous leukemia patients. Although an advantage is suggested by surrogate parameters, longer follow up is necessary to see if this translates into superior overall survival.
Topics: Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 22875617
DOI: 10.3324/haematol.2012.063172 -
Pharmacological Research Jan 2023Cucurbitacin B (CuB, CHO), the most abundant and active member of cucurbitacins, which are highly oxidized tetracyclic triterpenoids. Cucurbitacins are widely... (Review)
Review
Cucurbitacin B (CuB, CHO), the most abundant and active member of cucurbitacins, which are highly oxidized tetracyclic triterpenoids. Cucurbitacins are widely distributed in a variety of plants and mainly isolated from plants in the Cucurbitaceae family. CuB is mostly obtained from the pedicel of Cucumis melo L. Modern pharmacological studies have confirmed that CuB has a broad range of pharmacological activities, with significant therapeutic effects on a variety of diseases including inflammatory diseases, neurodegenerative diseases, diabetes mellitus, and cancers. In this study the PubMed, Web of Science, Science Direct, and China National Knowledge Infrastructure (CNKI) databases were searched from 1986 to 2022. After inclusion and exclusion criteria were applied, 98 out of 2484 articles were selected for a systematic review to comprehensively summarize the pharmacological activity, toxicity, and pharmacokinetic properties of CuB. The results showed that CuB exhibits potent anti-inflammatory, antioxidant, antiviral, hypoglycemic, hepatoprotective, neuroprotective, and anti-cancer activities mainly via regulating various signaling pathways, such as the Janus kinase/signal transducer and activator of transcription-3 (JAK/STAT3), nuclear factor erythroid 2-related factor-2/antioxidant responsive element (Nrf2/ARE), nuclear factor (NF)-κB, AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/Akt, cancerous inhibitor of protein phosphatase-2A/protein phosphatase-2A (CIP2A/PP2A), Wnt, focal adhesion kinase (FAK), Notch, and Hippo-Yes-associated protein (YAP) pathways. Studies of its toxicity and pharmacokinetic properties showed that CuB has non-specific toxicity and low bioavailability. In addition, derivatives and clinical applications of CuB are discussed in this paper.
Topics: Cucurbitacins; Protein Phosphatase 2; Antioxidants; Phosphatidylinositol 3-Kinases; Triterpenes; NF-kappa B
PubMed: 36460279
DOI: 10.1016/j.phrs.2022.106587 -
Journal of Cancer Research and Clinical... Nov 2009The objective of this analysis was to examine the relationship between genomic variation and health outcomes in studies performed in non-small cell lung cancer (NSCLC)... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The objective of this analysis was to examine the relationship between genomic variation and health outcomes in studies performed in non-small cell lung cancer (NSCLC) patients treated with single agent epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) using a systematic review with statistical pooling of data.
METHODS
We performed a systematic search of the literature using the MEDLINE, BIOSIS, and EMABASE databases from July 1997 to July 2007. Eligible studies were evaluated for quality and clinical, methodological, and statistical heterogeneity. Abstracted data judged to be sufficiently homogenous were pooled using a fixed effect model.
RESULTS
We found a statistically significant higher probability of tumor response (according to the RECIST criteria) for patients with EGFR mutations versus wild type (5.92, 95% CI 4.91-7.13) and patients with high- versus low EGFR protein expression (2.71, 95% CI 1.72-4.29). EGFR mutation and high EGFR protein expression were associated with significantly improved survival over the wild type and low protein expression groups (0.36, 95% CI 0.29-0.46 and 0.59, 95% CI 0.44-0.81), respectively. Last, there was a significant difference in EGFR-TKI treatment effect in the high EGFR gene copy number and high EGFR protein expression groups (0.72, 95% CI 0.57-0.92 and 0.53, 95% CI 0.35-0.80).
CONCLUSION
In conclusion, EGFR mutation and protein expression status may provide useful clinical information in terms of the likelihood of tumor response and disease prognosis. EGFR gene copy number and to a lesser extent, EGFR protein expression status, appear to be promising biomarkers for predicting a survival benefit with EGFR-TKI therapy in second line NSCLC, but further evidence is needed.
Topics: Carcinoma, Non-Small-Cell Lung; Data Interpretation, Statistical; ErbB Receptors; Gene Dosage; Humans; Lung Neoplasms; Mutation; Protein Kinase Inhibitors; Publication Bias; Randomized Controlled Trials as Topic
PubMed: 19430813
DOI: 10.1007/s00432-009-0595-3 -
Current Pharmaceutical Design 2021The antagonistic relationship between adenosine monophosphate-activated protein kinase (AMPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling...
Berberine Exerts Anti-cancer Activity by Modulating Adenosine Monophosphate- Activated Protein Kinase (AMPK) and the Phosphatidylinositol 3-Kinase/ Protein Kinase B (PI3K/AKT) Signaling Pathways.
BACKGROUND
The antagonistic relationship between adenosine monophosphate-activated protein kinase (AMPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling play a vital role in cancer development. The anti-cancer effects of berberine have been reported as a main component of the traditional Chinese medicine Rhizoma coptidis, although the roles of these signaling pathways in these effects have not been systematically reviewed.
METHODS
We searched the PubMed database for studies with keywords including ["berberine"] and ["tumor" or "cancer"] and ["AMPK"] or ["AKT"] published between January 2010 and July 2020, to elucidate the roles of the AMPK and PI3K/AKT pathways and their upstream and downstream targets in the anti-cancer effects of berberine.
RESULTS
The anti-cancer effects of berberine include inhibition of cancer cell proliferation, promotion of apoptosis and autophagy in cancer cells, and prevention of metastasis and angiogenesis. The mechanism of these effects involves multiple cell kinases and signaling pathways, including activation of AMPK and forkhead box transcription factor O3a (FOXO3a), accumulation of reactive oxygen species (ROS), and inhibition of the activity of PI3K/AKT, rapamycin (mTOR) and nuclear factor-κB (NF-κB). Most of these mechanisms converge on regulation of the balance of AMPK and PI3K/AKT signaling by berberine.
CONCLUSION
This evidence supports the possibility that berberine is a promising anti-cancer natural product, with pharmaceutical potential in inhibiting cancer growth, metastasis and angiogenesis via multiple pathways, particularly by regulating the balance of AMPK and PI3K/AKT signaling. However, systematic preclinical studies are still required to provide scientific evidence for further clinical studies.
Topics: AMP-Activated Protein Kinases; Adenosine Monophosphate; Berberine; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt
PubMed: 32988344
DOI: 10.2174/1381612826666200928155728 -
Cancer Reports (Hoboken, N.J.) Jan 2023Accumulating studies have evaluated the association between MAP3K1 polymorphisms and cancer prognosis. However, the results of these studies are conflicting. Given the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Accumulating studies have evaluated the association between MAP3K1 polymorphisms and cancer prognosis. However, the results of these studies are conflicting. Given the potential impact of MAP3K1 rs889312 SNP on the prognosis of various cancers, this meta-analysis was performed to obtain solid and credible evidence.
METHODS AND MATERIALS
This study was performed according to the PRISMA 2020 statement. A comprehensive article search was conducted to find and select articles from multiple databases, including PubMed, Google Scholar, Web of Science, EMBASE and the Cochrane Library, published up to 15th September 2022. The data analysis was performed with Review Manager v5.2. Pooled HR with its 95% CI and p-value was calculated where HR >1 suggests worse/poor survival and HR <1 suggests better survival of cancer patients.
RESULTS
A total of five articles comprising 24 439 patients were included for both qualitative and quantitative data synthesis. It was found that only the dominant genetic model (AC + CC vs. AA) showed a statistically significant poor overall survival for MAP3K1 rs889312 polymorphism (HR = 1.25, 95% CI = 1.06-1.47, p = .01). In addition, publication bias analysis by the Egger's test and the Begg-Mazumdar test reported no significant bias in the analysis of overall survival (p > .05).
CONCLUSIONS
The present study concludes that MAP3K1 gene rs889312 polymorphism plays a prognostic role in the survival of cancer patients. However, future research is recommended that will analyze more MAP3K SNPs along with rs889312, which may reveal more credible outcomes in terms of cancer prognosis.
Topics: Humans; Neoplasms; Polymorphism, Single Nucleotide; Prognosis; MAP Kinase Kinase Kinase 1
PubMed: 36560873
DOI: 10.1002/cnr2.1773 -
Cancer Letters Oct 2022p21-activated kinase 4 (PAK4), a member of the serine-threonine kinase family, was initially identified as a protein kinase that functions downstream of the Rho GTPases... (Review)
Review
p21-activated kinase 4 (PAK4), a member of the serine-threonine kinase family, was initially identified as a protein kinase that functions downstream of the Rho GTPases cdc42 and Rac1. Recently, it has been proven that PAK4 not only regulates many cellular physiological processes, but also plays an important role in the occurrence and development of various cancers. Here, we provide a systematic overview of PAK4, including its structure, localization, expression and aberration, upstream regulators, and key functions in almost every aspect of cancer hallmarks, including cancer cell proliferation, invasion and metastasis, angiogenesis, metabolism reprogramming, and immune escape. Subsequently, we also discuss the existing small molecule PAK4 inhibitors according to their structure types and their potential applications in cancer treatment. We hope our systematic review will provide the most comprehensive description of the current advancements in PAK4 research and new enlightenment for the individualized diagnosis and treatment of cancer.
Topics: Cell Proliferation; Humans; Neoplasms; Protein Kinases; Protein Serine-Threonine Kinases; p21-Activated Kinases
PubMed: 35798086
DOI: 10.1016/j.canlet.2022.215813 -
Breast Cancer (Tokyo, Japan) Jan 2018The introduction of specific cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors significantly improved progression-free survival in hormone receptor-positive metastatic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The introduction of specific cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors significantly improved progression-free survival in hormone receptor-positive metastatic breast cancer. CDK 4/6 inhibitors induce cell cycle arrest via liberating the tumor suppressor retinoblastoma protein from CDK4/6 inhibitory effect. Preliminary studies suggested an increase in the hematological toxicities which might affect the quality of life in such palliative setting.
METHODS
We searched PubMed, ASCO, ESMO and San Antonio meeting databases for randomized phase II/III trials in metastatic breast cancer receiving CDK4/6 inhibitors with safety data provided on the incidence of hematological adverse effects.
RESULTS
Our search identified 1012 citations that were screened for relevance. Thirty-six studies were found to be potentially eligible. After excluding the ineligible studies, six studies were deemed to be eligible for meta-analysis. The risk ratio (RR) was 11.31 [95% confidence interval (CI) 8.06-15.87; p < 0.0001] for all-grade leucopenia, 14.86 (95% CI 11.37-19.41; p < 0.0001) for all-grade neutropenia, 9.04 (95% CI 3.78-21.63; p < 0.0001) for all-grade thrombocytopenia and 3.57 (95% CI 2.65-4.81; p < 0.0001) for all-grade anemia. The RR for grade 3/4 leucopenia was 33.86 (95% CI 14.59-78.57; p < 0.0001), for grade 3/4 neutropenia was 44.00 (95% CI 24.72-78.33; p < 0.0001), for grade 3/4 thrombocytopenia was 5.70 (95% CI 2.03-16.01; p = 0.001) and for grade 3/4 anemia was 2.80 (95% CI 1.45-5.41; p = 0.002). There was no significant increase in the RR of febrile neutropenia with RR of 3.29 (95% CI 0.93-11.57; p = 0.06).
CONCLUSION
Our analysis provides evidence that the use of CDK 4/6 inhibitors is associated with an increased risk of all-grade and high-grade hematological adverse events, which seems to be a class-effect, but not of febrile neutropenia compared with hormonal therapy alone.
Topics: Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Drug-Related Side Effects and Adverse Reactions; Female; Hematologic Diseases; Humans; Prognosis; Protein Kinase Inhibitors
PubMed: 29147869
DOI: 10.1007/s12282-017-0818-4