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Advances in Health Sciences Education :... Dec 2022Professionals will increasingly be confronted with new insights and changes. This raises questions as to what kind of expertise professionals need, and how development... (Review)
Review
Professionals will increasingly be confronted with new insights and changes. This raises questions as to what kind of expertise professionals need, and how development of this expertise can be influenced within the contexts of both education and work. The terms adaptive expertise and adaptive performance are well-known concepts in the domains of education and Human Resource Development respectively. The literature, however, lacks a conceptual overview. Our research seeks to provide an overview on how adaptive expertise and adaptive performance are conceptualized. In addition we looked for what individual, task and organizational characteristics relate to adaptive expertise. We mined information drawn from existing reviews in an overview of reviews. Nine reviews met the inclusion criteria. Adaptive performance is best referred to as the visible expression of an adaptive expert and this is triggered by 'change'. The scope of this 'change' lies somewhere between change that is 'new for the learner' and change that is 'new for everyone in the whole world'. The extent to and way in which a learner or professional is able to deal with this change depends on the maturity of the learner or professional. We found numerous individual, task and environmental characteristics related to adaptive expertise and adaptive performance. The nature and relation of these characteristics, and their specificity in relation to adaptive expertise and adaptive performance are visualized in a figure, but also provide several suggestions for future research.
Topics: Humans; Educational Status; Workplace; Clinical Competence; Etoposide; Ifosfamide
PubMed: 36508136
DOI: 10.1007/s10459-022-10190-y -
Autophagy Aug 2021Induction of macroautophagy (hereafter termed autophagy) is a strategy to improve the outcome of antineoplastic therapies by facilitating the induction of immunogenic... (Review)
Review
Induction of macroautophagy (hereafter termed autophagy) is a strategy to improve the outcome of antineoplastic therapies by facilitating the induction of immunogenic cancer cell death and the consequent immune recognition of malignant cells. We analyzed 65,000 distinct compounds by means of a phenotypic discovery platform for autophagy induction and identified the IGF1R (insulin like growth factor 1 receptor) inhibitor picropodophyllin (PPP) as a potent inducer of autophagic flux. We found that PPP acts on-target, as an inhibitor of the tyrosine kinase activity of IGF1R and enhances the release of adenosine triphosphate, ATP, from stressed and dying cancer cells in vitro, thereby improving the therapeutic efficacy of chemoimmunotherapy in cancer-bearing mice. This PPP effect was phenocopied by another IGF1R inhibitor, linsitinib. Moreover, in human triple-negative breast cancer, phosphorylation of IGF1R correlates with reduced autophagy, an unfavorable local immune profile and poor prognosis. In summary, IGF1R inhibition may constitute a novel strategy for the treatment of cancer in the context of chemoimmunotherapy.
Topics: Animals; Autophagy; Cell Proliferation; Humans; Imidazoles; Podophyllotoxin; Protein Kinase Inhibitors; Pyrazines; Receptor, IGF Type 1
PubMed: 34110249
DOI: 10.1080/15548627.2021.1936934 -
Expert Opinion on Therapeutic Patents 2015Podophyllotoxin (PPT) is a naturally occurring antimitotic agent and an interesting lead in the development of anticancer agents. Its optimization led to the development... (Review)
Review
INTRODUCTION
Podophyllotoxin (PPT) is a naturally occurring antimitotic agent and an interesting lead in the development of anticancer agents. Its optimization led to the development of etoposide and teniposide used in combination chemotherapy with other anticancer drugs; unlike PPT these drugs act by inhibiting topoisomerases. Clinical success and toxicity issues at later stages of etoposide usage inclined researchers to develop structurally modified PPT derivatives. Some of the compounds obtained are under clinical investigations and are anticipated to reach the market.
AREAS COVERED
The present review summarizes the attempts made by researchers across the globe to find out newer anticancer agents based on the PPT structure. It brings out the outline of the inventions filed in the form of patents during the years 2012 - 2014.
EXPERT OPINION
After the successful development of etoposide and teniposide there has been considerable interest in the PPT skeleton to develop newer chemotherapeutic agents. In this regard, several PPT derivatives such as TOP53, GL331, NK611, F11782, and so on, have been developed and are undergoing clinical trials. However, its low natural abundance is a major problem in carrying out research on PPT skeleton. This issue is expected to be addressed with the development of newer synthetic strategies to access structurally modified PPTs.
Topics: Animals; Antineoplastic Agents; Drug Design; Humans; Neoplasms; Patents as Topic; Podophyllotoxin
PubMed: 26027947
DOI: 10.1517/13543776.2015.1051727 -
Natural Product Reports Sep 2022Covering: up to 2022Podophyllotoxin (PTOX, 1), a kind of aryltetralin-type lignan, was first discovered in the plant and its structure was clarified by W. Borsche and... (Review)
Review
Covering: up to 2022Podophyllotoxin (PTOX, 1), a kind of aryltetralin-type lignan, was first discovered in the plant and its structure was clarified by W. Borsche and J. Niemann in 1932. Due to its potent anti-cancer and anti-viral activities, it is considered one of the molecules most likely to be developed into modern drugs. With the increasing market demand and insufficient storage of natural resources, it is crucial to expand the sources of PTOXs. The original extraction method from plants has gradually failed to meet the requirements, and the biosynthesis and total synthesis have become the forward-looking alternatives. As key enzymes in the biosynthetic pathway of PTOXs and their catalytic mechanisms being constantly revealed, it is possible to realize the heterogeneous biosynthesis of PTOXs in the future. Chemical and chemoenzymatic synthesis also provide schemes for strictly controlling the asymmetric configuration of the tetracyclic core. Currently, the pharmacological activities of some PTOX derivatives have been extensively studied, laying the foundation for clinical candidate drugs. This review focuses primarily on the latest research progress in the biosynthesis, total synthesis, and pharmacological activities of PTOX and its derivatives, providing a more comprehensive understanding of these widely used compounds and supporting the future search for clinical applications.
Topics: Biosynthetic Pathways; Catalysis; Lignans; Podophyllotoxin
PubMed: 35913409
DOI: 10.1039/d2np00028h -
Medicinal Research Reviews Jan 2015Podophyllotoxin (PPT), as well as its congeners and derivatives, exhibits pronounced biological activities, especially antineoplastic effects. Its strong inhibitory... (Review)
Review
Podophyllotoxin (PPT), as well as its congeners and derivatives, exhibits pronounced biological activities, especially antineoplastic effects. Its strong inhibitory effect on tumor cell growth led to the development of three of the most highly prescribed anticancer drugs in the world, etoposide, teniposide, and the water-soluble prodrug etoposide phosphate. Their clinical success as well as intriguing mechanism of action stimulated great interest in further modification of PPT for better antitumor activity. The C-4 position has been a major target for structural derivatization aimed at either producing more potent compounds or overcoming drug resistance. Accordingly, numerous PPT derivatives have been prepared via hemisynthesis and important structure-activity relationship (SAR) correlations have been identified. Several resulting compounds, including GL-331, TOP-53, and NK611, reached clinical trials. Some excellent reviews on the distribution, sources, applications, synthesis, and SAR of PPT have been published. This review focuses on a second generation of new etoposide-related drugs and provides detailed coverage of the current status and recent development of C-4-modified PPT analogs as anticancer clinical trial candidates.
Topics: Animals; Antineoplastic Agents; Humans; Podophyllotoxin; Structure-Activity Relationship
PubMed: 24827545
DOI: 10.1002/med.21319 -
Current Medicinal Chemistry 2015
Topics: Antineoplastic Agents, Phytogenic; Biological Products; Camptothecin; Humans; Paclitaxel; Podophyllotoxin; Vinca Alkaloids
PubMed: 26502948
DOI: 10.2174/092986732230151019101908 -
Journal of Clinical Oncology : Official... Sep 2023Chemotherapeutic exposures are associated with subsequent malignant neoplasm (SMN) risk. The role of genetic susceptibility in chemotherapy-related SMNs should be...
PURPOSE
Chemotherapeutic exposures are associated with subsequent malignant neoplasm (SMN) risk. The role of genetic susceptibility in chemotherapy-related SMNs should be defined as use of radiation therapy (RT) decreases.
PATIENTS AND METHODS
SMNs among long-term childhood cancer survivors of European (EUR; N = 9,895) and African (AFR; N = 718) genetic ancestry from the Childhood Cancer Survivor Study and St Jude Lifetime Cohort Study were evaluated. An externally validated 179-variant polygenic risk score (PRS) associated with pleiotropic adult cancer risk from the UK Biobank Study (N > 400,000) was computed for each survivor. SMN cumulative incidence comparing top and bottom PRS quintiles was estimated, along with hazard ratios (HRs) from proportional hazards models.
RESULTS
A total of 1,594 survivors developed SMNs, with basal cell carcinomas (n = 822), breast cancers (n = 235), and thyroid cancers (n = 221) being the most frequent. Although SMN risk associations with the PRS were extremely modest in RT-exposed EUR survivors (HR, 1.22; = .048; n = 4,630), the increase in 30-year SMN cumulative incidence and HRs comparing top and bottom PRS quintiles was statistically significant among nonirradiated EUR survivors (n = 4,322) treated with alkylating agents (17% 6%; HR, 2.46; < .01), anthracyclines (20% 8%; HR, 2.86; < .001), epipodophyllotoxins (23% 1%; HR, 12.20; < .001), or platinums (46% 7%; HR, 8.58; < .01). This PRS also significantly modified epipodophyllotoxin-related SMN risk among nonirradiated AFR survivors (n = 414; < .01). Improvements in prediction attributable to the PRS were greatest for epipodophyllotoxin-exposed (AUC, 0.71 0.63) and platinum-exposed (AUC,0.68 0.58) survivors.
CONCLUSION
A pleiotropic cancer PRS has strong potential for improving SMN clinical risk stratification among nonirradiated survivors treated with specific chemotherapies. A polygenic risk screening approach may be a valuable complement to an early screening strategy on the basis of treatments and rare cancer-susceptibility mutations.
Topics: Adult; Child; Humans; Female; Cohort Studies; Cancer Survivors; Podophyllotoxin; Neoplasms, Second Primary; Breast Neoplasms; Risk Factors
PubMed: 37459583
DOI: 10.1200/JCO.23.00428 -
Japanese Journal of Radiology Dec 2023Cancer of the adolescent and young adult (AYA) generation has received increasing attention in recent years, however, there were few reports on radiotherapy for this... (Review)
Review
Cancer of the adolescent and young adult (AYA) generation has received increasing attention in recent years, however, there were few reports on radiotherapy for this area. As for pediatric cancer, many cancer of the AYA generation were treated with radiation therapy as the multidisciplinary treatment. In this article, we will review reproductive complications, which are considered to be particularly important complications of radiation therapy for AYA generation, and describe investigation of radiation therapy for cancers of the AYA generations at the Hyogo Cancer Center and the Hyogo Ion Beam Medical Center Kobe Proton Center. Germ cells are highly radiosensitive, and even low doses of radiation can cause infertility. Therefore, patients should be treated with sufficient knowledge to prevent fertility. Proton beam therapy for cancer of the AYA generation was useful therapy as pediatric cancer. However, proton beam therapy used less frequently. Insurance coverage, publicity, and access to facilities were considered issues for future study.
Topics: Child; Humans; Adolescent; Young Adult; Neoplasms; Etoposide; Fertility
PubMed: 37440159
DOI: 10.1007/s11604-023-01461-8 -
International Journal of Radiation... Mar 2023
Topics: Humans; Fast Neutrons; Neutrons; Brain Neoplasms; Carmustine; Etoposide; Radiotherapy Dosage; Boron Neutron Capture Therapy
PubMed: 36822785
DOI: 10.1016/j.ijrobp.2022.11.004 -
Biochemical and Biophysical Research... Aug 2019Neuroblastoma (NB) is a neuroendocrine tumor derived from neural crest cells. Approximately 90% of cases occur in children less than 5 years old. The amplification of...
Neuroblastoma (NB) is a neuroendocrine tumor derived from neural crest cells. Approximately 90% of cases occur in children less than 5 years old. The amplification of MYCN correlates with high-risk neuroblastoma and patients with MYCN amplified showed poorer prognosis than those without MYCN amplification. In this study, three compounds isolated from Juniperus oblonga showed anti-proliferative activity against NB cell lines with and without tetracycline inducible MYCN over-expression which were identified as (-)-deoxypodophyllotoxin (1), (-)-matairesinol (2) and (+)-isocupressic acid (3). The effects of compounds 2 and 3 in NB cells included a decrease in NB cell viability and induction of apoptosis. Compound 1 was more effective in NB cells over-expressing MycN. Compound 1 also showed almost 2-fold induction of intracellular free calcium levels in M2(+) cells, which may indicate a different mechanism of action for this compound. Cytotoxicity studies against the human embryonic kidney cell (HEK-293) showed compounds 1, 2 and 3 were ineffective in the non-cancer cells at concentrations approximating their IC against the NB cell lines. These results may lead to safer and more effective treatment options for NB patients especially for those with high-risk NB.
Topics: Antineoplastic Agents; Carboxylic Acids; Cell Line, Tumor; Cell Survival; Child, Preschool; Diterpenes; Drugs, Chinese Herbal; Furans; Gene Expression Regulation, Neoplastic; HEK293 Cells; Humans; Inhibitory Concentration 50; Juniperus; Lignans; Molecular Structure; N-Myc Proto-Oncogene Protein; Neuroblastoma; Phytotherapy; Plant Extracts; Podophyllotoxin; Tetrahydronaphthalenes
PubMed: 31255282
DOI: 10.1016/j.bbrc.2019.06.123